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Humphrey Department of Biomedical Engineering, Yale University, New Haven, USA, Center for Research & Innovation in Bioengineering, Valencia Polytechnic University, Valencia, Spain, Cardiovascular Research Center, Yale School of Medicine, New Haven, USA, Centro Nacional de Investigaciones Car‑ diovasculares Carlos III, Madrid, Spain, Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, USA Background: Marfan Syndrome is a primary cause of thoracic aortic aneurysms; it arises from dysfunctional fibrillin-1, which normally sta- bilizes elastic fibers and promotes smooth muscle mechano-sensing of the matrix. Despite significant advancements, clear correlations between microstructural integrity and aortic functionality remain wanting. Biaxial stress-stretch curves (A) and circumferential stiffness vs. elastin Methods: Age-matched wild-type, Fbn1C1041G/ + [1], and Fbn1mgR/ porosity (B) for the ascending thoracic aorta of the analyzed Marfan mgR [2] mice represented three stages of disease severity. Experi- mice. Dilatation and circumferential stiffness from the G&R model (C). ments quantified specimen-specific thoracic aortopathy in terms of: (1) mechanical metrics from ex vivo biaxial testing that were described References by a four-fiber family hyperelastic model [3]; (2) microstructural met - [1] Milewicz DM, et al. Marfan syndrome. Nat Rev Dis Primers. 2021;7(1):64. rics[4] from ex vivo multiphoton microscopy including elastin poros- [2] Pereira L, et al. Pathogenetic sequence for aneurysm revealed in mice ity, density, and engagement of collagen fibers and cells; (3) cardiac underexpressing fibrillin‑1. PNAS. 1999;96(7):3819–23. function from in vivo ultrasound and µCT imaging. Material proper- [3] Judge DP, et al. Evidence for a critical contribution of haploinsufficiency ties were incorporated within a mechanobiologically equilibrated in the complex pathogenesis of Marfan syndrome. J Clin Invest. constrained mixture model of arterial growth and remodeling (G&R) 2004;114(2):172–81. [5]. The analysis assessed long-term impacts of locally compromised [4] Cavinato C, Chen M, Weiss D, Ruiz‑Rodríguez MJ, Schwartz MA, Humphrey elastin integrity, cellular mechanosensing and mechanoregulation, JD. Progressive Microstructural deterioration dictates evolving biome‑ collagen turnover, and endothelial function on disease progression chanical dysfunction in the Marfan aorta. Front Cardiovascular Medicine. through perturbations to the initial homeostatic state. 2021;8:1904. Results: Aortic dilatation correlated strongly with key mechanical met- [5] Latorre M, Humphrey JD. Numerical knockouts–In silico assessment of rics of compromised aortic functionality as well as with elastin defects, factors predisposing to thoracic aortic aneurysms. PLoS Comput Biol. collagen remodeling, and altered cellular function. Variable dilatations 2020;16(10). at a given age reflected a “pseudo-time” of progressive deterioration consistent with a progressive anoikis. The G&R model reproduces the Keywords: Marfan syndrome, Biaxial mechanics, Microstructure, same trends in aortic dilatation, stored energy, and circumferential Growth and remodeling, Aneurysms stiffness with increasing losses of elastic fiber integrity. The progressive © The Author(s) 2022. 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Artery Research O.2 Methods: To address this need, we applied mechanical stimulations Impaired β2‑adrenergic endothelium‑dependent vasodilation on human aortic SMC in culture at passage 6–7, by using the Flex- is reversed by phosphodiesterase inhibition in patients previously cell tension system (Fig. 1A). We tried different durations of stimu- hospitalized with COVID‑19 lation (24 h, 48 h, 72 h, and 100 h) versus unstimulated control. We chose 7 genes, coding for contractile proteins of the cytoskeleton 1 1 1 1 Dr. Luca Faconti , Ms Bushra Farikh , Dr. Ryan J McNally , Dr Sally Brett , (Fbn1, ACTA2), extracellular matrix components (Coll1A1, LAMA5), or Prof. Philip J Chowienczyk involved in activation/regulation of traction forces (TGFBR1, MYLK), King’s College London, London, United Kingdom and in cell differentiation (TAGLN). The expression of these genes was quantified with qPCR analysis, relatively to a reference gene (HPRT) Background: Endothelial dysfunction may underlie many of the com- (Fig. 1B). plications of COVID-19 [1]. The pulse wave response to salbutamol Results: We observed that: 1. From 72 h of stimulation, the difference (PWRS)—change in the augmentation index, AIx- provides a means between stimulated and control groups is the most significant; 2. For to assess endothelial vasodilator function mediated through the nitric the majority of the genes, their expression decreases with the stimula- oxide-cyclic guanosine monophosphate pathway (NO-cGMP) [2,3]. tion; 3. The basal medium enhances α-SMA production. Nevertheless, Here we aim to determine whether PWRS is abnormal in patients due to the low quantity of RNA available, we had to repeat cell stimu- recovered from COVID-19. lation, and reach n = 3 repetitions for each group during the qPCR Methods: We examined PWRS in subjects previously hospitalized analysis for more accurate results. with COVID-19, those recovered from mild symptoms and seronega- Conclusions: We were able to quantify SMC mechanosensitivity and tive controls (absence of SARS-CoV-2-antibodies) with similar risk fac- mechanotransduction. AoSMC seem to modulate their gene expres- tors for cardiovascular disease. In a sub-sample, we also assessed the sion after 72 h of stimulation. As future work, we would like to investi- response in the presence and absence of the phosphodiesterase type gate the influence of intercellular signaling under stimulation. 5 inhibitor sildenafil which inhibits the breakdown of cGMP. Results: 101 subjects (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Inhaled salbutamol reduced AIx in controls (n = 34) and those recov- ered from mild symptoms of COVID-19 (n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] − 2.85 [− 5.52, − 0.188] %, − 2.32 [− 5.17, 0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symp- toms and those previously hospitalised respectively (P = 0.001). In a sub-sample (n = 22), sildenafil enhanced the response to salbutamol (change in AIx 0.05 [− 2.15, 2.24] vs. − 3.96 [− 7.01, − 2.18], P = 0.006) with no significant difference between hospitalized (n = 12) and non- hospitalized subjects (n = 10). Conclusions: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function which can be ame- liorated by sildenafil. (A) Control group and stimulated group with Flexcell tension system. (B) Results of the qPCR analysis on all groups for 7 genes (cDNA quan- References tity, relatively to a reference gene (HPRT )). [1] Libby P, Lüscher T. COVID-19 is, in the end, an endothelial disease. Eur. Heart J. 2020;41:3038–3044. References [2] Chowienczyk PJ, Kelly RP, MacCallum H, Millasseau SC, Anders- 1. Michel J‑B, Jondeau G, Milewicz DM. From genetics to response to injury: son TLG, Gosling RG, Ritter JM, Änggård EE. Photoplethysmographic vascular smooth muscle cells in aneurysms and dissections of the assessment of pulse wave reflection: Blunted response to endothe - ascending aorta. Cardiovasc Res. 2018;114(4):578–89. lium-dependent beta2-adrenergic vasodilation in type II diabetes mel- 2. Milewicz DM, Trybus KM, Guo D, Sweeney HL, et al. Altered Smooth litus. J. Am. Coll. Cardiol. 1999;34:2007–2014. Muscle Cell Force Generation as a Driver of Thoracic Aortic Aneurysms [3] Wilkinson IB, Hall IR, Maccallum H, Mackenzie IS, Mceniery CM, and Dissections. Arteriosclerosis, Thrombosis, and Vascular Biology. Arend BJ Van Der, Shu Y, Mackay LS, Webb DJ, Cockcroft JR. Clinical 2016;116:303229. Evaluation of a Noninvasive, Widely Applicable Method for Assessing 3. Liu M, Gomez D. Smooth Muscle Cell Phenotypic Diversity. Arterioscler Endothelial Function. 2002; Thromb Vasc Biol. 2019;39(9):1715–1723. 4. Humphrey JD, Schwartz MA, Tellides G, Milewicz DM. Role of Mechanotrans‑ Keywords: COVID-19, Endothelium, AIx duction in Vascular Biology: Focus on Thoracic Aortic Aneurysms and Dissections. Circulation Research. 2015;116(8):1448–61. O.3 Keywords: Cell biomechanics, Epigenetics, Mechanical stimulation, How does mechanical stress affect gene expression in human qPC aortic smooth muscle cells? 1 1 2 Mme Claudie Petit , Amira Ben Hassine, Mireille Thomas , 2 1 Alain Guignandon , Pr. Stéphane Avril O.4 Pentosan polysulfate, an aggrecanase inhibitor modulates Mines Saint‑Etienne, Université de Lyon, INSERM, U 1059 SAINBIOSE, arterial stiffness in spontaneously hypertensive rats Saint‑Etienne, France, Université Jean Monnet, Université de Lyon, 1 2 3 INSERM, U 1059 SAINBIOSE, Saint‑Etienne, France Miss Aleksandra Klosinska , Dr Keith Siew , Mr Tao L uo , 4 1 5 5 Mrs Nichola Figg , Mrs Sarah Cleary , Dr Isam Sharif , Mr Colin Williams , Background: SMC modulate their phenotype in response to envi- 1 3 Professor Ian Wilkinson , Professor Michael Sutcliffe , Professor Kevin ronmental conditions, as in for instance ascending thoracic aortic 1 1 O’Shaughnessy , Dr Y Yasmin aneurysms (ATAA) (1–3). It was previously shown that missensing of University of Cambridge, Department of Medicine, EMIT Division, mechanical stimuli plays a major role in ATAA (2,4). Nevertheless, there Cambridge, United Kingdom, University College London, Department is a pressing need to better quantify the mechanobiological behaviour of Renal Medicine, London, United Kingdom, University of Cambridge, of SMCs. A rtery Research Department of Engineering, Cambridge, United Kingdom, University whether healthy adults (controls, n = 36) or patients with moderate of Cambridge, Department of Medicine, Cardiovascular Division, Cam‑ chronic kidney disease (CKD, n = 30) were analyzed respectively with bridge, United Kingdom, Covance CRS Limited, Huntingdon, United paired or independent samples t-tests. Kingdom Results: Despite similar cd-PWV and cr-PWV, rd-PWV at baseline was significantly lower in CKD than in controls (3.6 ± 1.4 m/s vs. Background: Arterial stiffness is an independent predictor of all-cause 4.5 ± 1.8 m/s, p = 0.024), but this difference faded (p = 0.145) after and cardiovascular mortality in many populations. Our recent research adjustment for age. Post NTG, brachial blood pressure decreased and showed that loss of aggrecan integrity associates with age-related heart rate increased similarly between groups. Rd-PWV increased in arterial stiffening (ARAS) in humans1, and others have shown that inhi- controls (from 4.62 ± 1.49 m/s to 5.94 ± 2.29 m/s, p < 0.001) and in CKD bition of ADAMTS/aggrecanase enzymes, which degrade aggrecan, (from 3.71 ± 1.60 m/s to 5.18 ± 2.12 m/s, p < 0.001), in a similar extent improves cardiac function 2. Currently, there are no drugs that specifi- (interaction p = 0.111). However, cd-PWV significantly increased post- cally target arterial stiffening in humans. We hypothesise that ADAMTS NTG only in the CKD group (p = 0.009). inhibitor, Pentosan Polysulfate (PPS), represents an attractive molecule Conclusions: This technique, adapted by our team for small conduit that can be repurposed as a first-in-class drug treatment for ARAS. arteries, may broaden our understanding of the consequences of the inversion of the stiffness gradient. Methods: We performed an in vivo pharmacological experiment using 15wk-old spontaneous hypertensive male rats (SHR) that were admin- References istered either PPS or vehicle control (n = 7 per group) subcutaneously 1. Obeid H, Fortier C, Garneau CA, Pare M, Boutouyrie P, Bruno RM, et al. 3 times per week for 4 weeks. Animals were sacrificed and fully intact Radial‑ digital pulse wave velocity: a noninvasive method for assess‑ aortae including blood, cartilage, etc. were harvested and stored at ing stiffness of small conduit arteries. Am J Physiol Heart Circ Physiol. − 800 °C. Arterial wall thickness, stress-strain and failures stress were 2021;320(4):H1361‑H9. measured, and tensile elasticity calculated ex vivo. 2. Fortier C, Garneau CA, Pare M, Obeid H, Cote N, Duval K, et al. Modulation of Results: Preliminary analysis showed that PPS significantly reduced Arterial Stiffness Gradient by Acute Administration of Nitroglycerin. Front aortic wall thickening normally associated with arterial stiffening in Physiol. 2021;12:774056. hypertension (Vehicle 225 ± 6 µm vs 204 ± 6 µm, p = 0.0143). PPS also decreased aortic stiffening significantly at supraphysiological pres- Keywords: Chronic kidney disease, Nitroglycerin, Arterial stiffness gra- sures in treated rats, and treated rats had a higher failure stress relative dient, Small conduit arteries to vehicle controls. Conclusions: This proof-of-principle study demonstrated that an O.6 aggrecanase inhibitor can modulate aortic stiffness markers in SHR, Characterization of internal jugular vein region‑specific but the short treatment period may not be adequate to reveal clini- distension during progressive volume loading cally significant differences. Further longitudinal studies are therefore, 1 1,2 2 needed to establish if longer exposure to PPS can reduce aortic stiff- Mr Jeremy N. Cohen , Mr Eric T. Hedge , Dr Danielle K. Greaves , 1,2 3 1 ness at clinically significant levels in older animals. Dr Andrew D. Robertson , Dr Lonnie G. Petersen , Dr Jason S. Au Department of Kinesiology and Health Sciences, University Of Waterloo, References Waterloo, Canada, Schlegel‑University of Waterloo Research Institute [1] Yasmin et al. The matrix proteins aggrecan and fibulin‑1 play a key role in for Aging, University of Waterloo, Waterloo, Canada, Department determining aortic stiffness. Sci Rep. 2018 Jun 4;8(1):8550. https:// doi. org/ of Aeronautics and Astronautics, Massachusetts Institute of Technology, 10. 1038/ s41598‑ 018‑ 25851‑5. Cambridge, United States of America [2] Vistnes M. et al. Penstisan polysulfate decreases myocardial expression of the extracellular matrixenzyme ADAMTS4 and improves cardiac function Background: The internal jugular vein (IJV) is highly compliant with in vivo rates subjected to pressure overload by aortoc banding. PLOS One roles in intracranial blood flow and pressure regulation. The dynamic and 2014: 9, e8923. https:// doi. org/ 10. 1371/ journ al. pone. 00896 21. variable nature of venous flow, especially during changes in gravitational stress, leads to non-linear geometry. However, the impact of this irregu- Keywords: Arterial stiffness, Aggrecan, Pentosan polysulfate, Sponta- lar anatomy on IJV distension during progressive volume loading is not neous hypertensive rats understood and may contribute to adverse flow profiles, a component of Virchow’s triad for thrombotic risk. We characterized IJV 3D shape and volume expansion during progressive head-down tilt (HDT), a micro- O.5 gravity analogue. Radial‑digital pulse wave velocity: stiffness of small conduit Methods: We recruited 5 healthy, young adults (2 females, 25 ± 4 year, arteries increases after nitroglycerin administration 168 ± 8 cm, 68 ± 15 kg). Using an ultrasound probe tracked in 3D 1,2 1 1 space, we captured right IJV cross-sectional area (CSA) from clavicle to Dr Catherine Fortier , Charles‑Antoine Garneau , Mathilde Paré , 1 1 1 2 mandible. Progressive cephalad fluid shift was achieved by HDT at 0°, Dr Hasan Obeid , Nadège Côté , Karine Duval , Dr Rémi Goupil , − 6°, − 15°, and − 30°, each held for 5 min. CSA were traced at 0.3 cm Dr Mohsen Agharazii intervals from caudal to cranial and vein volume calculated by cylindri- Chu De Québec Research Center ‑ Université Laval, Québec, Canada, cal CSA. CIUSSS NIM‑ Sacré Coeur de Montréal, Montréal, Canada Results: Progressive HDT significantly altered IJV distension, demon- 2 2 strating stepwise effects on average CSA (0.89 ± 0.4cm , 1.26 ± 0.6cm , Background: The alteration of the physiological stiffness gradient 2 2 2 1.68 ± 0.7cm , 2.02 ± 1cm ; P = 0.003, η = 0.67) and total volume within larger vessels would increase the transmission of greater pul- (4.0 ± 1.5 mL, 5.8 ± 3.3 mL, 7.6 ± 4.2 mL, 9.3 ± 5.4 mL; P = 0.007, satility to the microcirculation, thus explaining the damage to the η = 0.63) through HDT conditions 0°, − 6°, − 15°, − 30°, respectively. pressure-sensitive organs. We aimed to describe the response of small Caudal regions displayed greater distension capacity compared to cra- conduit arteries of the hand (radial-digital PWV, rd-PWV) (1) following nial across conditions (P < 0.001). the pharmacological alteration of the stiffness gradient using nitro - Conclusion: Our precise 3D volume measures demonstrate the IJV can glycerin. (2). accommodate significant fluid shifts through a large range in disten- Methods: Simultaneous application of piezoelectric sensors (Com- sion ability, beyond stimuli mimicking microgravity. Irregular expan- plior) at the level of the carotid (c), the radial artery (r) and the tip sion patterns in the caudal regions may lend to flow abnormalities and of the index finger (d) was used to calculate the rd-PWV, before and requires investigation to ascertain prognostic value of IJV geometry on 4 min after a sublingual administration of 0.4 mg of NTG. Changes in thrombotic risk. arterial stiffness pre-post NTG and comparisons between two groups Artery Research Reference Fayon A, Menu P & El Omar, R. Cellularized small‑ caliber tissue‑ engineered vascular grafts: looking for the ultimate gold standard. npj Regen Med. 2021 Aug (6), 46 Keywords: Tissue-engineered vascular graft, Human umbilical cord, Inside-out, Artery bypass models, Vascular Tissue Engineering O.8 Inhibition of atherosclerotic plaque calcification by Omega‑3 polyunsaturated fatty acids through the resolvin E1 receptor ChemR23 1 1 PhD Gonzalo Ar tiach , PhD Andres Laguna‑Fernandez , 1 1 1,2 PhD Miguel Carracedo , PhD Hildur Arnardottir , Prof. Magnus Bäck Department of Medicine, Karolinska Institutet, Stockholm, Sweden, Theme Heart and Vessels, Karolinska University Hospital, Stockholm, Sweden Fig. 1 Internal jugular vein cross‑sectional area from caudal to cranial Background: The immune cell response in atherosclerotic plaques is regions normalized to individual neck length (A) and total cylindrical vein characterized by an impaired resolution of inflammation (1). Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator derived from volume during progressive head‑ down tilt (B) omega-3 polyunsaturated fatty acids (PUFA) has been shown to play Keywords: Microgravity, Venous, 3D a critical role in atherosclerosis by promoting the resolution of the inflammation (2). The aim of the present study was to unravel the role of omega-3 PUFA, RvE1 and the RvE1 receptor ChemR23 in the process O.7 of atherosclerotic plaque calcification. New approach in the design of a human tissue engineered Methods: Fat-1 transgene (Fat-1tg), which enables the endogenous pro- vascular graft and preliminary studies in arterial bypass models duction of n-3 PUFA, was inserted in apolipoprotein E (ApoE)-deficient in the pig mice, in combination or not with genetic deletion of ChemR23. Calcifi- 1 1 2 Dr Adrien Fayon , Mrs Deborah Helle , Dr Véronique R egnault , cation was assessed by Alizarin Red staining and macrophage markers 3 3 2,4 Dr Marc Ponçot , Pr Isabelle R oyaud , Pr Jean‑Pablo Maureira , were assessed by immunohistochemistry in aortic root sections. 4 5 1 1 Dr Dan Pan , Dr Caroline Gaucher , Pr Patrick M enu , Dr Reine El Omar Results: Our results show that 72 week old Fat-1tg × Apoe -/- mice 1 2 Université de Lorraine, CNRS, IMoPA, F‑54000 Nancy, France, Uni‑ developed less atherosclerotic plaque calcification compared with versité de Lorraine, Inserm, DCAC, F‑54000 Nancy, France, Université Apoe-/- mice (0–3% vs 4–8%, p < 0.001). Moreover, deletion of de Lorraine, CNRS, IJL, F‑54000 Nancy, France, Université de Lorraine, ChemR23 enhanced atherosclerotic plaque calcification (4–13% CHRU‑Nancy, Service de Chirurgie Cardiovasculaire, F‑54000 Nancy, vs. 4–8%, p < 0.001), and this effect was not reversed by the pres- France, Université de Lorraine, CITHEFOR, F‑54000 Nancy, France ence of Fat-1tg (4–14% vs. 4–8%, p < 0.001). Furthermore, the Fat- 1tg × Apoe-/- mice had significantly higher expression of the M2 Background: Arterial bypass surgery of small-caliber vessels using macrophage marker Arg1 compared with Apoe-/- mice (17.4 ± 2.5% synthetic vascular prostheses remains inefficient as they promote vs 5.1 ± 1.5%; p < 0.0001), which was reversed by genetic dele- thrombosis probably due to a low or non-functionalization of their tion of ChemR23 (5.0 ± 1.1% vs. 17.4 ± 2.5%; p < 0.0001 vs internal surface(1). As a potential therapeutic alternative, we have Fat-1tg × Apoe -/- mice). developed a human cellularized TEVG (tissue-engineered vascular Conclusion: These results suggest that the beneficial effects of Fat- graft) whose components are all derived from the umbilical cord. 1tg were mediated through ChemR23. Hence, omega-3 PUFA may Methods: Decellularized umbilical arteries were coated at their lumi- have a therapeutic potential for reducing atherosclerotic plaque cal- nal surface with an extracellular matrix extracted from Wharton’s cification through RvE1-signaling by means of ChemR23. jelly and then cellularized by mesenchymal stromal cells derived also from WJ. The luminal coating and cellularization were optimized by References an innovative "inside-out" method allowing easy access to the lumi- 1. Bäck M, Yurdagul A, Tabas I, Öörni K and Kovanen PT. Inflammation and its nal surface. TEVG hemocompatibility (Thrombin Generation Assay) resolution in atherosclerosis: mediators and therapeutic opportunities. and mechanical properties (burst pressure test, stress rupture test, Nat Rev Cardiol. 2019 Jul;16(7):389–406. dynamic mechanical analysis) were evaluated. Preliminary in vivo 2. Carracedo M, Artiach G, Arnardottir H and Bäck M. The resolution of inflam‑ implantations were conducted in pigs for coronary or femoral arterial mation through omega‑3 fatty acids in atherosclerosis, intimal hyperpla‑ bypass. sia, and vascular calcification. Semin Immunopathol. 2019;41:757–766. Results: The “inside-out” method, which did not impact mechanical properties of the TEVG, allowed a homogeneous cellularization of Keywords: Atherosclerosis, Calcification, Omega-3, Resolvin arteries luminal surface confirming its adaptability to a vascular con- text. Hemocompatibility assays showed that the TEVG behaves as a native blood vessel due to full cell covering of the luminal surface. The TEVG was successfully implanted in a coronary artery bypass O.9 model (n = 1), and was well tolerated, colonized and remain pat- Reduced Micromechanical Stiffness of Large Diameter Abdominal ent for 2 weeks post-implantation in a femoral replacement model Aortic Aneurysm (AAA) Wall Tissue (n = 1). 2 2 2 1 Martin Hossack , Robert Fisher, Francesco Torella , Jillian Madine , Conclusion: Our TEVG is an allogeneic therapeutic solution offering Riaz Akhtar a ready-to-use graft that may supply a tissue bank and which can be 1 2 grafted by minimally invasive robotic techniques avoiding an invasive University of Liverpool, United Kingdom, Liverpool University Hospitals surgery, having beneficial societal and economic impacts. NHS Foundation Trust, United Kingdom A rtery Research Introduction: Use of a maximum diameter threshold as the sole O.10 indicator for aneurysm repair risks rupture during surveillance in Reservoir‑wave parameters and cardiovascular prediction: higher-risk cases, and unnecessary repair in others [1]. Here, we Analysis of the population‑based CARTaGENE cohort characterised the micromechanical properties of aneurysmal aortic 1,4 2,3 Dr Louis‑Charles Desbiens , Dr Catherine Fortier , Dr Annie‑Claire tissues with the aim of identifying high-risk cases and directing spe- 1,4 2,4 5 Nadeau‑Fredette , Dr François Madore , Dr Bernhard Hametner , cific management. 5 3,6 2,4 Dr Siegfried Wassertheurer , Dr Mohsen Agharazii , Dr Rémi Goupil Methods: Full thickness anterior aortic wall tissue samples were 1 2 Hôpital Maisonneuve‑Rosemont, Montréal, Canada, Hôpital du harvested from 16 patients undergoing repair of degenerative AAA. Sacré‑Coeur de Montréal, Montréal, Canada, CHU de Québec—Univer‑ Nanoindentation was used to determine the shear storage modulus sité Laval, Québec, Canada, Université de Montréal, Montréal, Canada, (G′). We performed indentations on tissue cross-sections in 3 lay- 5 6 AIT Austrian Institute of Technology, Vienna, Austria, Université Laval, ers (inner, middle, outer). At least 4 samples were tested from each Québec, Canada patient. In total, there were 102 samples (1269 indentations). We stratified micromechanical findings according to maximum trans- Background: The reservoir-wave concept hypothesizes that blood verse diameter (MTD), established through interrogation of pre- pressure is the sum of a reservoir and an excess pressure. Nevertheless, operative contrast-enhanced CT scans. the clinical association of reservoir-wave parameters with cardiovascu- Results & Discussion: Aortic wall tissue demonstrated a pattern lar outcomes remains controversial. of reducing stiffness from the inner to middle (median 31.5 kPa vs Methods: We studied individuals aged between 40 and 69 from the 24.4 kPa, P < 0.05) and middle to outer layers (24.4 kPa vs 13.1 kPa, CARTaGENE cohort (Canada). Radial waveforms were measured with P < 0.05). Wall stiffness increased as MTD increased from 50–59 mm aplanation tonometry (SphygmoCor). They were transformed to cen- to 60–69 mm (median 20.7 kPa vs 29.5 kPa, P < 0.05). At 70-79 mm, tral waveforms using generalized transfer functions and used to gen- wall stiffness reduced (median 22 kPa, NS), and reduced further erate reservoir parameters (Reservoir pressure [RP], Reservoir pressure as MTD exceeded 80 mm (median 19.6 kPa, P < 0.05) (Fig. 1). The integral [RPI], Excess pressure [XSP], Excess pressure integral [XSPI], mechanical properties of vascular tissues depend largely on the Systolic rate constant [SC], Diastolic rate constant [DC], Optimized extracellular matrix. A reduced G′, observed in larger diameter aneu- asymptotic pressure [PInf]). Major adverse atherosclerotic events rysms may indicate a failure in the collagen network, predisposing (MACE: cardiovascular death, stroke, myocardial infarction) during a to rupture. 10-year follow-up were obtained using medico-administrative data- Conclusion: At higher MTD, AAA wall loses stiffness at larger diam- bases. Associations of reservoir parameters with MACE were derived eters. The work can be translated to identify individuals with high- using crude and fully adjusted Cox models. Incremental predictive risk AAA. performance over the ASCVD score (atherosclerotic cardiovascular dis- ease score; using revised pooled cohort equations) for each reservoir parameter was displayed using c-statistic improvement and continu- ous net reclassification indexes (NRI). Results: From 17,629 individuals, 2327 had a MACE during the fol- low-up. All reservoir parameters were significantly higher in patients who experienced a MACE. After full adjustment, RP, XSPI and DC were associated with increased MACE incidence ( Table). Spline anal- ysis did not reveal any non-linear relationships between reservoir parameters and MACEs. When added to the ASCVD prediction score, XSP and DC significantly improved c-statistics while RP, XSPI, DC and PInf led to a significant net reclassification improvement. Conclusion: Reservoir parameters, especially the diastolic rate con- stant, improve cardiovascular prediction in a population-based cohort. Table Fig. 1 Shear storage modulus shown as a function of maximum trans‑ verse diameter Reference 1.Polzer, S., Gasser, T.C., Vlachovský, R., Kubíček, L., Lambert, L., Man, V., Novák, K., Slažanský, M., Burša, J. and Staffa, R., 2020. Biomechanical indices are more sensitive than diameter in predicting rupture of asympto‑ O.11 matic abdominal aortic aneurysms. Journal of vascular surgery, 71(2), Histomorphometric analysis of cell and matrix components pp.617–626. of ascending thoracic aortic aneurysm 1,2 3 4 2 Berta Ganizada , Shaiv Parikh , Mitch Ramaekers , Armand Jaminon , Keywords: abdominal aortic aneurysms, maximum diameter, biome- 2 1 5 Asim Cengiz Akbulut , Ehsan Natour , Ryan Accord , Joachim Ernst chanics, vascular Artery Research 4 1 1 3 1 Wildberger , Simon Schalla , Jos M aessen, Reesink , Elham Bidar , Age and weight are represented as mean ± SD and other values as Leon Schurgers. median with IQR [Q1-Q3]. Department of Cardiothoracic Surgery, Maastricht University Medical 2 References Centre + , Maastricht, The Netherlands, Department of Biochemistry, 1. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis Cardiovascular Research Institute Maastricht, Maastricht University, 3 and treatment of aortic diseases: Document covering acute and chronic Maastricht, The Netherlands, Department of Biomedical Engineer‑ 4 aortic diseases of the thoracic and abdominal aorta of the adult. The Task ing, Maastricht University, Maastricht, The Netherlands, Department Force for the Diagnosis and Treatment of Aortic Diseases of the European of Radiology and Nuclear Medicine Cardiology, Maastricht University 5 Society of Cardiology (ESC) [published correction appears in Eur Heart J. Medical Centre + , Maastricht, The Netherlands, Department of Pediatric 2015 Nov 1;36(41):2779]. Eur Heart J. 2014;35(41):2873–2926. and Congenital Cardiothoracic Surgery, University Medical Center Gronin‑ 2. Cebull HL, Rayz VL, Goergen CJ. Recent Advances in Biomechanical Charac‑ gen, Groningen, The Netherlands. terization of Thoracic Aortic Aneurysms. Front Cardiovasc Med. 2020;7:75 Background: Current indication for ascending thoracic aortic aneu- Keywords: Ascending aorta, Aneurysms, ECM-VSMC, Arterial rysm (aTAA) surgery is based on aortic diameter of 5–5.5 cm or a remodeling growth rate of > 0.5 cm/year [1]. However, current screening surveil- lance and risk estimation simplifies the complexity of aTAA disease, which might lead to a high-risk open-chest cardiac surgery [2]. Our O.12 aim was to examine ex vivo histological features of aTAA specimens, C–C chemokine ligand 5 from subcutaneous adipose tissue to assess changes in extracellular matrix (ECM) content and vascular has a central role in vascular aging smooth muscle cell ( VSMC) properties. Laura Le Pelletier Methods: Surgical samples of the ventral aspect of the ascending UMRS938 Inserm Saint Antoine Research Center, Paris, France aorta were collected from patients suffering from aTAA (n = 20) and patients with non-aneurysmal coronary bypass or stenotic valve sur- Background: Adipose tissue (AT) has a critical role in cardiovascular gery which served as controls (n = 10). Medial cross-sectional thick- diseases – particularly through its secretory activity. Aging is associ- ness, collagen/elastin content, and VSMC number were determined ated with AT redistribution, senescence, and changes in the secretome by quantitative histomorphometry. In addition, immunohistochemi- (1,2). We have previously shown that human adipose stromal cells cal markers of VSMC phenotype, α-smooth muscle actin (α-SMA), (ASCs) from the subcutaneous AT (SCAT) of aged women display calponin-1 (CNN1), and S100 calcium binding protein A4 (S100A4) senescence and oxidative stress (3). We hypothesized that the ASC were assessed. Image quantification analysis was performed using secretome contributes to the onset of endothelial dysfunction, an QuPath. early stage in vascular aging. Results: Aneurysmal aortas showed increased elastin fragmentation Methods: Conditioned media were prepared from ASCs isolated and regionally more dense collagen I/III confirming medial degenera- from SCAT of healthy young (< 25y) or aged (> 60y) women. ASCs’ tion. This resulted in a marked rise in collagen-to-elastin ratio (Table 1). secretome were added to human coronary artery endothelial cells. Medial cross-sectional thickness and number of VSMCs were increased C–C-chemokine-ligand-5 (CCL5) was identified by an adipokine array. in aneurysmal aortas (Table 1). Expression of α-SMA and CNN1 The expression of CCL5 in SCAT from men with coronary disease was decreased significantly, whilst S100A4 expression was not different evaluated. The effect of a CCL5 receptor antagonist, maraviroc, was between the groups (Table 1). investigate in peripheral blood mononuclear cells (PBMCs) in HIV- Conclusions: Our preliminary results support the notion of an infected individuals from two studies. imbalanced interaction between ECM-VSMCs that may play a cru- Results: The secretome of aged-donor ASCs induced endothelial cial role in arterial remodeling cascade, leading to aTAA formation. cell dysfunction and senescence. We showed that CCL5 was respon- Further research is needed with the ultimate aim to guide clinical sible for these effects and corroborate in experiments with recom- management. binant protein and maraviroc. We observed that CCL5 expression in SCAT of patients with coronary heart disease was strongly associated with blood pressure. Moreover, maraviroc prevented endothelial cell dysfunction in vitro and reverted PBMC senescence in HIV-infected individuals. Conclusions: Our results highlighted the ability of the CCL5 secreted by aged ASCs from SCAT to induce endothelial dysfunction and senes- cence—both of which are early steps in vascular aging—and a poten- tial link between these phenomena and hypertension. References 1.Stout MB, Justice JN, Nicklas BJ, Kirkland JL. Physiological Aging: Links Among Adipose Tissue Dysfunction, Diabetes, and Frailty. Physiol Bethesda Md. janv 2017;32(1):9‑19. 2.Liu Z, Wu KKL, Jiang X, Xu A, Cheng KKY. The role of adipose tissue senes‑ cence in obesity‑ and ageing‑related metabolic disorders. Clin Sci Lond Engl 1979. 31 janv 2020;134(2):315‑30. 3.Le Pelletier L, Mantecon M, Gorwood J, Auclair M, Foresti R, Motterlini R, et al. Metformin alleviates stress‑induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction. eLife. 21 sept 2021;10:e62635. Keywords: Aging, adipose tissue, endothelial dysfunction, adipose stromal cells A rtery Research O.13 (PeriCam PSI NR System, Perimed). Post-occlusive reactive hyper- Cardiovascular risk in adolescents translates into lower carotid emia (PORH) was assessed following a standardized protocol and intima‑media thickness and better distensibility in young data were analyzed with a signal processing software (PIMSoft, Per- adults—The KiGGS2‑cohort imed). The amplitude of PORH responses was expressed as a per- 1,2,3 2,3 1 centage increase between peak and baseline perfusion (%). Karsten Königstein , Julia Büschges , Arno SchmidtT ‑ rucksäss , 2,3 Results: Twenty-nine individuals (14 patients with prediabetes and Hannelore Neuhauser 15 controls) were studied. There wasn’t any statistically significant 1 2 University of Basel, Basel, Switzerland, Robert‑Koch Institute, Berlin, difference regarding age, sex, body mass index and blood pres- Germany, DZHK (German Centre for Cardiovascular Research), Berlin, sure levels between the two groups. At baseline, skin microvascu- Germany lar perfusion was significantly higher in patients with prediabetes compared to controls (50.9 ± 11.5 vs. 39.2 ± 8.7, p = 0.006) while Background: Lifestyle-associated cardiovascular risk may be elevated during occlusion, perfusion was similarly reduced in both groups. already during adolescence translating into an increased disease Post occlusion reperfusion was significantly lower in the prediabetes burden in adulthood. The KiGGS cohort characterizes cardiovascular group as compared to the controls (145.0 ± 42.8 vs. 195.2 ± 47.3% aging from childhood until young adulthood in the German general respectively, p = 0.007). population. This study analyzes the effects of increased cardiovascular Conclusions: We showed, for the first time, that individuals with risk during adolescence on carotid properties in young adults. prediabetes demonstrated skin microvascular dysfunction, that may Methods: 1,545 participants of the representative healthy popula- reflect a more generalized microvascular damage. tion sample of the national KiGGS-0 cohort (10–17 years of age) had carotid ultrasound-assessment 10 years later at the KiGGS-2 follow-up References (20–28 years of age). A cardiovascular risk score (CV-R) was calculated 1. Lamparter J, Raum P, Pfeiffer N, Peto T, Höhn R, et al. Prevalence and associa‑ at KiGGS-0 including variables of arterial hypertension, obesity, dyslipi- tions of diabetic retinopathy in a large cohort of prediabetic subjects: The demia and smoking. Carotid intima-media thickness (CIMT) and dis- Gutenberg Health Study. J Diabetes Complications. 2014;28(4):482–7. tensibility (DC) at KiGGS-2 were associated with CV-R. 2. Friedman A, Marrero D, Ma Y, Ackermann R, Narayan KMV, et al. Value of Results: Unfavorable alterations of all components of CV-R were urinary albumin‑to ‑ creatinine ratio as a predictor of type 2 diabetes in associated with higher CIMT and/or reduced DC. Relative risks for pre‑ diabetic individuals. Diabetes Care. 2008;31(12):2344–8. pathologically elevated CIMT ≥ 90th percentile and/or decreased 3. de Matheus AS, Clemente ELS, de Lourdes RM, Torres VDC, Gomes MB, et al. DC ≤ 10th percentile were elevated in participants with ‘intermedi- Assessment of microvascular endothelial function in type 1 diabetes ate’ (RRCIMT = 1.89 [1.23–2.91], p < 0.05; RRDC = 1.27 [0.79–2.06]) or using laser speckle contrast imaging. J Diabetes Complications. 2017, ‘high’ risk (RRCIMT = 1.83 [0.95–3.52], p < 0.1; RRDC = 1.76 [0.93–3.32], 31(4):753–7. p < 0.1) according to CV-R. Conclusions: If an intermediate or high cardiovascular risk according Keywords: prediabetes, microcirculation dysfunction, LASCA to CV-R is apparent in adolescence, signs of early vascular aging may occur at a very young age. The promotion of a favorable lifestyle to reduce risk factor burden even in the overall healthy general popula- tion at a young age seems to be crucial for primary prevention of car- O.15 diovascular diseases. Arterial Stiffness Assessment by Pulse Arrival Time: An In Silico Proof of Concept. Keywords: carotid intima-media thickness (cIMT ), primary prevention, 1 2 1 Jingyuan Hong , Manasi Nandi , Jordi Alastruey. cardiovascular risk, adolescents School of Biomedical Engineering & Imaging Sciences, King’s College London, London, UK, School of Cancer & Pharmaceutical Sciences, King’s O.14 College London, London, UK Evaluation of skin microvascular dysfunction with Laser Speckle Contrast Analysis in prediabetes Arterial stiffness (AS) is one of the primary symptoms of vascu- 1 1 2 lar ageing (1). Stiffer arteries lead to increased pulse wave velocity Stamatina Lamprou , Nikolaos Koletsos , Ioanna Zografou , 3 1 (PWV ) and decreased pulse transit time (PTT ). PWV is considered the Gesthimani Mintziori , Konstantinos Mastrogiannis , 2 1 1 clinical gold standard for the diagnosis of AS, but direct measure- Michael Doumas , Eugenia Gkaliagkousi , Areti Triantafyllou. ment in daily life is challenging (2). Pulse arrival time (PAT), which Third Department of Internal Medicine, Papageorgiou General Hospital, consists of the pre-ejection period (PEP) and PTT, is defined as the Aristotle University of Thessaloniki, Thessaloniki, Greece, Second Prope‑ time interval between the R-peak of electrocardiogram (ECG) and deutic Department of Internal Medicine, Hippokration General Hospital, a characteristic point of photoplethysmogram (PPG) (3,4). Since Aristotle University of Thessaloniki, Thessaloniki, Greece, Unit of Repro‑ most standard wearable devices can capture PPG and ECG signals, ductive Endocrinology, 1st Department of Obstetrics and Gynecology, and PAT correlates highly with vascular properties, such as vascu- Papageorgiou General Hospital, Aristotle University of Thessaloniki, lar tone, PAT extracted from wearable signals has the potential to Thessaloniki, Greece indicate cardiovascular health (5). The study used a database of in silico pulse wave signals for 4,374 virtual subjects to calculate aor- Objectives: Prediabetes is recognized as a significant metabolic tic PWV (aPWV), aortic-radial PTT (arPTT ), and PEP (6). The strength status, being a key factor in the occurrence of diabetes mellitus of the correlation between PAT and aPWV was assessed using the (DM). There is increasing evidence concerning microvascular com- correlation coefficient (R2). Relative sensitivity analysis was used to plications in prediabetes most commonly in skin, kidneys and ret- investigate the effects of cardiac and vascular properties on PAT. The ina (1,2). Laser speckle contrast analysis (LASCA) is a non-invasive R2 value between PAT and aPWV was 0.84. The inverse relationship technique that can be used to evaluate skin microvascular func- between PAT and aPWV illustrates that stiffer arteries resulted in tion. Previous studies have shown skin microvascular dysfunction in decreased PAT, even when considering specific age groups. Accord- patients with DM (3). However, to our knowledge, no previous study ing to the relative sensitivity analysis, PAT is mainly affected by has evaluated skin microcirculation, using LASCA, in patients with stroke volume and PWV. Our in silico study suggests that PAT has the prediabetes. potential to be used as a marker for assessing the arterial stiffening Methods: In all subjects, forearm skin blood flow was recorded component of vascular ageing. under standardized conditions using a laser speckle contrast imager Artery Research Results: In the overall population (n = 7924, 54.2% women, age 18–82 years), the prevalence of HVA/NVA/EVA was 7.8/68.1/24.1%, respectively, with EVA prevalence increasing in older age. NVA and EVA, as compared to HVA, were independently associated with anthropometric (BMI), metabolic (HbA1c), psychosocial (family sta- tus) and lifestyle (pack years, alcohol intake) factors, on top of age, gender, and blood pressure (Figure). Additional associations with VA categories were found in younger and older age (level of education), in middle age (income), and in older age (lack of physical activity). Conclusions: In this large population-based study we found a high percentage of early vascular aging, with a significant increase with increasing age. Psychosocial and lifestyle factors seem to play an independent role. Schematic representation of the definition of pulse arrival time (Back - ground), the extraction method of pulse transit time and pre-ejection period (Methodology), and arterial stiffness analysis of pulse arrival time (Result). References 1. Olsen MH, Angell SY, Asma S, Boutouyrie P, et al. The Lancet. 2016 Nov;388(10060):2665–712. 2. Willum Hansen T, Staessen JA, Torp‑Pedersen C, Rasmussen S, et al. Circula‑ Keywords: Vascular aging tion. 2006 Feb;113(5):664–70. 3. Zhang G, Gao M, Xu D, Olivier NB, Mukkamala R. Journal of Applied Physiol‑ ogy. 2011 Dec;111(6):1681–6. 4. Zheng YL, Ding XR, Poon CCY, Lo BPL, et al. IEEE Trans Biomed Eng. 2014 O.17 May;61(5):1538–54. Hydrochlorothiazide, but not chlortalidone nor furosemide, 5. Zheng YL, Yan BP, Zhang Y T, Poon CCY. Ann Biomed Eng. 2015 enhances vascular calcification in CKD rats with mineral bone Sep;43(9):2242–52. disorder 6. Charlton PH, Mariscal Harana J, Vennin S, Li Y, Chowienczyk P, Alastruey J. 1 1 1 1 Mohsen Agharazii , Richard Larivière , Roth‑Visal Ung , Sylvain Picard , Am. J. Physiol.‑Heart Circ. Physiol. 2019 Nov;H1062–85. 1 1 1 Dailson N. de Souza , Darren E. Richard , Fabrice Mac‑Way Chu De Québec‑université Laval, Québec, Canada Keywords: Vascular ageing, Arterial stiffness, Pulse arrival time, Pulse wave velocity, Wearable signals Background: Previously, we reported that hydrochlorothiazide (HCTZ)-based regimen aggravated arterial calcification and stiff- O.16 ness in a rat model of chronic kidney disease (CKD) with mineral and Prevalence and determinants of vascular aging: the LEAD study. bone disorder (MBD). In this study, we investigated if all diuretic- 1 2 2 based treatments aggravate of arterial stiffness and calcification in Kathrin Danninger , Otto Burghuber , Marie‑Kathrin Breyer , 2 2 2 CKD-MBD rats. Patricia Puchhammer , Alina Ofenheimer , Robab Breyer‑Kohansal , 3 2 1 Methods: In rats with renal mass ablation-induced CKD, MBD Christoph Kaufmann , Sylvia Hartl, Thomas Weber was generated by a Ca/P-rich diet and calcitriol. The animals were Klinikum Wels‑Grieskirchen, Department of Cardiology, Linz, Austria, divided into four groups; (1) CKD-MBD control; (2) CKD-MBD + HC TZ 2 3 Ludwig‑Boltzmann‑Institute for Lung Diseases, Vienna, Austria, Klinikum (thiazide diuretic, 5 mg/kg/d); (3) CKD-MBD + Chlor thalidone (thi- Ottakring, Department of Cardiology, Vienna, Vienna azide-like diuretic, 5 mg/kg/d), and; (4) CKD-MBD + Furosemide (loop diuretics, 10 mg/kg/d). At week 6, systolic and mean blood Background: Vascular aging (VA) is an important and prognostically pressure (SBP and MBP), pulse pressure (PP) and pulse wave velocity relevant aspect of biological aging. Its determinants are incompletely (PWV) were determined invaisively. Thoracic aorta calcification was understood, and a holistic view is missing. assessed by von Kossa staining. Methods: The LEAD (Lung, Heart, Social, Body) study is an ongoing, Results: SBP was reduced by all types of diuretics. Contrary to chlo- longitudinal, population-based observational study, which started rtalidone and furosemide, HCTZ treatment led to a reduction of in 2011 in Vienna and six villages from Lower Austria. As part of the MBP, but an increase in PP and PWV in CKD-MBD rats (p < 0.05). As study, cfPWV was measured non-invasively using applanation tonom- expected from these hemodynamic changes, medial calcification in etry (SphygmoCor device, Atcor medical). In a predefined healthy nor - the thoracic aorta was significantly greater in CKD-MBD rats treated mal population (non-smokers without known hypertension, diabetes, with HCTZ as compared to all the other groups of rats (p < 0.05). hyperlipidemia, or cardiovascular disease, free from antihypertensive Conclusions: In rats with CKD-MBD, HCTZ, but not other types of and lipid-lowering medication, blood pressure of < 130/85 mmHg), diuretic, exacerbated arterial stiffness and vascular calcification age-specific Z-scores for cfPWV were calculated. Healthy VA (HVA), nor - despite a reduction in SBP. The deleterious effect of HCTZ in CKD- mal (NVA) and early (EVA) VA was defined as cfPWV value < 10th, 10th- MBD rats may have major clinical impact as this diuretic is widely 90th, and > 90th percentile, respectively. use in patients with CKD that often develop MBD. A rtery Research The figures shows blood pressure (systolic, mean, diastolic, pulse pres- sure), and aortic stiffness by pulse wave velocity (PWV), and aortic calcifi- cation by von Kossa staining. Keywords: Chronic kidney disease, mineral bone disease, vascular calcification O.18 Results are adjusted for age, race-study center, body mass index, dia- Relationships between excessive daytime sleepiness, arterial betes, heart rate, mean arterial pressure, and blood-pressure medica- stiffness, and physical activity. The Atherosclerosis Risk tion use. AHA: American Heart Association: T: tertile. in Communities (ARIC) Study References Michael A Newton, Rachael Hamm, Emma Barinas‑Mitchell, Pamela L 1. Blachier M, Dauvilliers Y, Jaussent I et al. Excessive daytime sleepiness and Lutsey, Hirofumi Tanaka, Kapuaola Gellert, Lee Stoner, Michelle Meyer vascular events: the Three City Study. Ann Neurol. 2012;71(5):661–7. University of North Carolina at Chapel Hill, Chapel Hill, United States, 2. Lee CH, Ng WY, Hau W et al. Excessive daytime sleepiness is associated with University of North Carolina at Chapel Hill, Chapel Hill, United States, longer culprit lesion and adverse outcomes in patients with coronary 3 4 University of Pittsburgh, Pittsburgh, United States, University of Minne‑ artery disease. J Clin Sleep Med. 2013;9(12):1267–72. sota Twin Cities, Minneapolis, United States, University of Texas at Austin, 3. Li J, Covassin N, Bock JM et al. Excessive Daytime Sleepiness and Cardiovas‑ Austin, United States, University of Hawaii, Honolulu, United States, cular Mortality in US Adults: A NHANES 2005–2008 Follow‑Up Study. Nat University of North Carolina at Chapel Hill, Chapel Hill, United States, Sci Sleep. 2021;13:1049–59. University of North Carolina at Chapel Hill, Chapel Hill, United States Keywords: Arterial stiffness, sleep, physical activity, older adults Background: Excessive Daytime Sleepiness (EDS) is associated with higher risk of cardiovascular disease (CVD) events (1,2) and mortal- ity (3). However, the association between EDS and subclinical CVD, O.19 such as arterial stiffness, is not fully understood nor is the role of Greater intrinsic arterial wall stiffness and its unfavourable physical activity (PA) in this association. We examined the relation- trajectory over time in type 2 diabetes ship between EDS and arterial stiffness, measured using carotid- 1 1 1 Kunihiko Aizawa , Phillip E Gates , David M Mawson , femoral pulse wave velocity (cfPWV), with PA as a potential effect 1 1 1 2,3 Francesco Casanova , Kim M Gooding , Suzy V Hope , Isabel Goncalves , modifier. 2 4 5 6 Jan Nilsson , Faisel Kahn , Helen M Colhoun , Andrea Natali , Carlo Methods: A cross-sectional analysis of ARIC Study participants 7 1 Palombo , Angela C Shore (n = 2349, mean age: 79.6, 57.2% female, 19.2% black adults) who underwent cfPWV measures (VP-1000 Plus, Omron Co., Kyoto, 1 NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Japan) and completed the Epworth Sleep Scale (ESS) and Baecke 2 Exeter, United Kingdom, Department of Clinical Sciences, Lund Univer‑ questionnaires in 2016–2019. EDS was defined as ESS ≥ 11. We 3 sity, Malmö, Sweden, Department of Cardiology, Skåne University Hospi‑ calculated moderate-vigorous PA (min/week) and categorized PA 4 tal, Malmö, Sweden, Division of Systems Medicine, University of Dundee, based on the distribution and guidelines. We used multivariable 5 Dundee, UK, Centre for Genomic and Experimental Medicine, University linear regression to estimate the association between ESS, EDS, 6 of Edinburgh, Edinburgh, UK, Department of Clinical and Experimental and cfPWV, and evaluated effect modification by PA. Results are 7 Medicine, University of Pisa, Pisa, Italy, Department of Surgical, Medical, presented as beta coefficients (β) and 95% confidence intervals Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy (CI). Results: A total of 14.4% participants reported EDS. The association Background: A greater central artery stiffness is observed in people of ESS and EDS with cfPWV differed by PA level. The association of ESS with type 2 diabetes (T2DM). However, it is unclear about intrinsic arte- (Figure A) and EDS (Figure B) with cfPWV became more negative with rial wall stiffness in these patients. We aimed to determine the utility higher PA levels, although the associations with EDS were not statistically of β cross-sectionally and longitudinally in T2DM. METHODS: We stud- significant. ied 753 adults with T2DM (DM+: 67.5 ± 8.3 years, 227F) and 436 adults Conclusion: A negative association was observed between ESS without T2DM (DM−: 67.0 ± 9.2 years, 159F) cross-sectionally (Phase 1), and cfPWV at the most intense level of PA in older adults. In and subsequently studied 310 adults in DM + (68.6 ± 7.6 years, 104F) those not meeting PA guidelines, other adverse life and partici- and 210 adults in DM− (67.6 ± 8.5 years, 83F) over three years longitu- pant characteristics could outweigh the effects of ESS and EDS on dinally (Phase 2). Carotid-femoral pulse wave velocity was measured, cfPWV. and its data were used to calculate β as previously described . o Artery Research 1 1 1 1 Results: In Phase 1, β was significantly greater in DM+ than DM− Garcia‑Peña , Amaya Fernández‑Celis , Alicia Gainza , Virginia Álvarez , 1 1 1 after adjusting for age and sex [27.5 (26.6–28.3) vs 23.6 (22.4–24.8) Rafael Sádaba , Natalia López‑Andrés , Eva Jover García au, p < 0.001]. Partial correlation analyses after adjusting for age and 1 Cardiovascular Translational Research, Navarrabiomed, Hospital Univer‑ sex found that β was significantly associated with HbA1c (r = 0.15 sitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, p < 0.001) and heart rate (r = 0.23 p < 0.001) in DM+. I Phase 2, percent- Pamplona, Spain, Pamplona, Spain age changes in β were significantly greater in DM + than DM− [19.5 (14.9–24.0) vs 5.0 (− 0.6–10.6) %, p < 0.001] after adjusting for age, sex Background: The pathophysiological role of angiogenesis and lym- and baseline β . Multivariable linear regression analyses revealed that phangiogenesis in aortic stenosis (AS) remains unknown. Valve the percentage changes in β were independently associated with avascularity is seemly abrogated in AS and neovascularization is well- percentage changes in heart rate in DM + (overall R = 0.19). correlated with the disease(1,2). We study sex-related differences in Conclusion: β was greater in DM + than DM−. Furthermore, β angiogenesis and lymphangiogenesis in aortic valves (AVs) and valve o o changed over three years with ageing but it changed much more in interstitial cells (VICs) from AS patients. DM + than DM−. These data suggest that intrinsic arterial wall stiff- Methods: 226 patients recruited (60.6% men) with severe AS undergo- ness may be a useful target for therapeutic intervention. ing surgical valve replacement. Results: The density of total neovessels was higher in AVs from men Reference versus women’s. Small and medium neovessels were more abundant Spronck et al. J Hypertens 2017;35:98–104. in men’s AVs. Male AVs exhibited enhanced CD31 and VE-cadherin expressions. Levels of the pro-angiogenic markers [vascular endothe- Keywords: Ageing, Aorta, Blood pressure, Heart rate lial growth factor (VEGF)-A, VEGF receptor (VEGFR)1, VEGFR2, insu- lin-like growth factor-binding protein-2 (IGFBP-2), interleukin (IL)-8, chemerin and fibroblast growth factor (FGF)-7] were increased in O.20 men’s AVs. Transforming growth factor-β expression was higher in The bidirectional longitudinal relationships between arterial male AVs. Expression of antiangiogenic molecules [thrombospondin stiffness and hypertension and those between arterial stiffness (Tsp)-1, endostatin and CD36] was upregulated in male AVs, although and diabetes mellitus the levels of Tsp-2, IL-4, IL-12p70 and chondromodulin-1 were similar Professor Hirofumi Tomiyama between sexes. The number of lymphatic vessels and the expression of the lymphangiogenic markers Lyve-1 and D2-40 was enhanced in Japan, Suginami, Japabn men’s AV also VEGF-C, VEGF-D and VEGFR3. VICs isolated from men’s Background: Hypertension and diabetes mellitus frequently coex- AVs secreted higher amounts of pro-angiogenic (VEGF-A, VEGFR1, ist; however, it has not yet been clarified if the bidirectional longi- IGFBP-2 and FGF-7) and pro-lymphangiogenic factors (VEGF-C, VEGF- tudinal relationships between arterial stiffness and hypertension D and VEGFR3) than women’s without changes in antiangiogenic are independent of those between arterial stiffness and diabetes markers. mellitus. Conclusions: We show that aberrant angiogenic and lymphangio- Methods: In this 16-year prospective observational study, 3960 genic cues are over-represented in male AVs. VICs are a relevant source middle-aged employees of a Japanese construction company with- of multiple morphogens involved in angiogenesis and lymphangi- out hypertension/diabetes mellitus at the study baseline underwent ogenesis likely endowing the AV of men with the predominant calcific annual repeated measurements of the blood pressure, serum glyco- AS phenotypes (3,4). sylated hemoglobin A1c level (HbA1c), and brachial-ankle pulse wave velocity (baPWV ). References Results: By the end of the study period, 664, 779, 154, and 406 1. Collett GD, Canfield AE. Angiogenesis and pericytes in the initiation of subjects developed hypertension, prehypertension, diabetes ectopic calcification. Circ Res. 2005;96(9):930–8. mellitus, and prediabetes, respectively. Increased baPWV at the 2.Rajamannan NM, et al. Calcified rheumatic valve neoangiogenesis is associ‑ baseline was associated with a significant odds ratio (per 1 stand- ated with vascular endothelial growth factor expression and osteoblast‑ ard deviation increase) for new onset of prehypertension/hyper- like bone formation. Circulation. 2005;111(24):3296–301. tension with (2.45/3.28, P < 0.01) or without (2.49/2.76, P < 0.01) 3.Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples coexisting prediabetes/diabetes mellitus, but not for new onset hypertrophic cartilage remodeling, ossification and angiogenesis during of prediabetes/diabetes mellitus without coexisting hypertension. endochondral bone formation. Nat Med. 1999;5(6):623–8. Analyses using the latent growth curve model confirmed the bi- 4.Nelson V, Patil V, Simon LR, Schmidt K, McCoy CM, Masters KS. Angiogenic directional relationships between baPWV and hypertension, but Secretion Profile of Valvular Interstitial Cells Varies With Cellular Sex and no such relationship was observed between baPWV and abnormal Phenotype. Front Cardiovasc Med. 2021;8:736303. glucose metabolism. Conclusions: In middle-aged Japanese subjects in contrast to the Keywords: Aortic-stenosis, sex, angiogenesis, lymphangiogenesis bi-directional relationships that exist between arterial stiffness and hypertension, increased arterial stiffness preceding the development of diabetes mellitus may represent that associated with the develop- O.22 ment of hypertension, as it is observed only in cases of diabetes mel- Arterial stiffness predicts sustained hypertension in patients litus coexisting with hypertension. Therefore, arterial stiffness may be with high normal blood pressure/grade 1 hypertension associated to a greater degree with the development of hypertension 1,2 1 1 Dr. Enrique Rodilla , Dr. Andrea Mendizábal , Dr. Iratxe Jiménez , than with the development of diabetes mellitus. 1 1 1 Dr. Leticia Pérez , Dr. Sergio Canales , Dr. Alicia Roldán , Dr. Santiago Keywords: arterial stiffness; hypertension 1 1 1 2 Pintos , Dr. Marta Catalán , Dr. María‑Carmen Sáez , Dr. José Chordá , Dr. José‑Antonio Costa O.21 1 2 Hospital Universitario de Sagunto, Puerto De Sagunto, Spain, Universi‑ Characterization of the sex‑specific pattern of angiogenesis dad Cardenal Herrera‑CEU, CEU Universities, Moncada, Spain and lymphangiogenesis in aortic stenosis 1 1 Background: 2018 ESC-ESH Guidelines for the Management of Arte- Lara Matilla Cuenca , Ernesto Martín‑Núñez , Mattie Garaikoetxea 1 1 1 1 rial Hypertension recommend pharmacological treatment if patients Zubillaga , Adela Navarro , Julieta Anabela Vico, Vanessa Arrieta , Amaia A rtery Research with grade 1 HTN at low-moderate risk remain hypertensive after a period of lifestyle intervention. Our objective was to assess the pre- dictive value of early vascular aging (EVA) to identifying patients who developed sustained HTN after baseline diagnosis. Methods: Retrospective, descriptive, longitudinal study including all consecutive patients referred to a HTN Unit with suspected naïve HTN without prior pharmacological treatment. EVA was defined accord- ing to estimated pulse wave velocity (brachial oscillometry, Mobil- O-Graph (IEM ) in seven age-groups(1). Standard clinical tests were performed at baseline and after 12 months. Results: Since 2010, 335 consecutive patients entered the study, with 201 women (60%), a mean age of 46,4 years (± 13), mean office BP of 130/76 (± 12/9), and ambulatory BP of 122/78 (± 8/7) mmHg. Distri- bution of BP was 155 (46.3%) patients with high-normal BP, 28 (8,4%) with white-coat HTN, 108 (32.2%) with masked HTN and 44 (13.1%) with established HTN. At baseline, 57% of patients showed EVA, after a mean time of 1.1 year, 65% of participants presented elevated ABPM. A selection of Survey Results In univariate analysis, baseline stiffness (EVA) was associated with ele - vated ABPM-values in the follow-up visit (OR: 2.0; IC 1.3–3.1; p = 0.003). Keywords: Survey, Knowledge, Awareness, Vascular age After adjustment for age, gender and pulse pressure, baseline EVA kept its significant predictive value (OR:2.6; IC 1.6–4.2; p = 0.001). O.25 Conclusions: Arterial damage characterized as EVA according to esti- Early vascular aging associated with sympathetic hyperactivity mated PWV by brachial oscillometry doubles the probability of sustained in obese hypertensive individuals with moderate to severe HTN one year after initial assessment in naïve patients with high-normal obstructive sleep apnea BP/grade 1 HTN at low-moderate risk. 1 1 1 Samanta Mattos , Michelle Rabello Cunha , Marcia Regina Simas Klein , Reference Mario Neves Nunan D, Fleming S, Hametner B, Wassertheurer S. Performance of pulse wave State University of Rio de Janeiro, Rio de Janeiro, Brazil velocity measured using a brachial cuff in a community setting. Blood Press Monit. 2014;19:315–9. Background: Obstructive sleep apnea (OSA) is an independent cardi- ovascular risk (CVR) factor. The objective was to evaluate sympathetic Keywords: Early vascular aging (EVA), risk stratification, pulse wave tone and vascular disease in obese hypertensive with moderate and velocity, high-normal blood pressure severe OSA. Methods: Individuals of both sexes, aged 40–70 years and body mass index (BMI) ≥ 30 and < 40 kg/m2, submitted to assessment of O.23 heart rate variability (HRV), central parameters by Mobil-O-Graph and Awareness and perceptions of health care providers carotid ultrasound. Sleep study was performed through a portable and researchers on vascular ageing: Quantitative Survey Results. home sleep test device (WatchPAT ). 1 2 5 4 Chloe Park , Andrie Panayiotou, Thomas Weber , Christopher Mayer , Results: Patients (n = 49) were divided into two groups based on 3 6 Areti Triantafyllou , Rachel Climie the apnea–hypopnea index (AHI): absent-mild (AM) group (AHI < 15 MRC Unit for lifelong Health and Ageing at UCL, London, United King‑ events/h, n = 17) and moderate-severe (MS) group (AHI ≥ 15 dom, Cyprus International Institute for Environmental and Public Health, events/h, n = 32). The mean BMI was similar (35 ± 3 vs 34 ± 2 kg/ Cyprus University of Technology, Limassol, Cyprus, Medical School, m2, p = 0.248). Systolic blood pressure (120 ± 15 vs 131 ± 14 mmHg, Aristoteleio University Thessaloniki, Thessaloniki, Greece, AIT Austrian p = 0.003), pulse pressure (43 ± 9 vs 49 ± 8 mmHg, p = 0.011), CVR Institute of Technology GmbH, Vienna, Austria, Cardiology Department, (6.8 ± 4.1 vs 14.4 ± 10.7%, p = 0.003) and cardiometabolic age Klinikum Wels‑Grieskirchen, Wels, Austria, Menzies Institute for Medical (48 ± 6 vs 52 ± 8 years, p = 0.034) were higher in the MS group. The Research, University of Tasmania, Hobart, Australia same group presented higher low frequency/high frequency (LF/ HF) ratio (0.83 ± 0.56 vs 1.91 ± 1.98, p = 0.017), pulse wave veloc- Introduction: Vascular Age (VA) can assess cardiovascular disease risk, ity (PWV) (7.1 ± 0.7 vs 8.0 ± 1.2 m/s, p = 0.003), vascular age (50 ± 6 independently of chronological age, however it is not yet widely applied vs 56 ± 8 years, p = 0.014) and carotid intima-media thickness in routine clinical practice. A quantitative questionnaire was developed (0.58 ± 0.09 vs 0.70 ± 0.12 mm, p = 0.001). PWV was significantly cor - to assess current knowledge gaps related to VA and barriers to imple- related with LF/HF ratio (r = 0.609, p < 0.001) only in the MS group. mentation in routine practice in both research and clinical settings. Conclusion: In this sample of obese hypertensive patients, moderate Methods: Using a stepwise mixed-methods approach, a quantitative to severe OSA was associated with sympathetic hyperactivity and evi- questionnaire was constructed. The 22-item anonymous survey was dence of early vascular aging with increased arterial stiffness and sub - based on a previous qualitative analysis including 80 participants with clinical atherosclerosis. multiple scientific backgrounds, and included questions on perceptions/ beliefs, knowledge, and implementation of VA. The survey was dissemi- Reference nated to clinicians and researchers world-wide, via social media and tar- Bironneau V, Tamisier R, Trzepizur W, et al. Sleep apnoea and endothelial dys‑ geted emails from well-known societies (including Artery, ESH, ISH, ESC). function: An individual patient data meta‑analysis. Sleep Med Rev. 2020 Results: 276 (50% female) completed the questionnaire, 46% were clini- Aug;52:101–309. cians, 33% researchers, 10% students. Clinical specialties included cardi- ology (36%), internal medicine (22%) and General Practice (10%). While Keywords: Hypertension; Sleep apnea; Obesity; Arterial stiffness 84% of clinicians and researchers rate VA importance as high or very high (Table), only 11% of clinicians measure VA in clinical settings. Limiting factors include cost, lack of guidelines and lack of knowledge. Discussion: These results show that implementation of VA is very low in clinical settings and awareness of VA needs to be improved via planned targeted awareness strategies and educational material. Artery Research O.26 pressure-diameter tests were performed at 95/100/105% of Acute vasopressin neutralization with the aptamer NOX‑F37 the < i > in vivo < /i > axial stretch and axial force –length tests at improves immediately cardiac but not peripheral endothelial 10/60/100/140 mmHg. Data were fit using a nonlinear constitutive dysfunction in rats with chronic heart failure model [1]. 1 1 1 1 Results: Figure (bar char ts, < i > n < /i > = 4–8 per group) shows pas- Yohan Stephan , Marina Hamrouche , Lise Charrier , Lionel Nicol , 2 2 1 1 sive metrics calculated at < i > in vivo < /i > axial stretch and group- Marie‑Laure Ozoux , Philip Janiak , Jeremy Bellien , Paul Mulder specific systolic blood pressures [2]. AngII caused larger increases in 1 2 Inserm U1096, Rouen, France, Corteria Pharmaceuticals, Paris, France wall thickness than NE. Both NE and AngII led to significant struc - tural arterial stiffening, driven by a combination of wall thickening Background: Vasopressin is one of the leading pathophysiologi- and stiffening of the wall material. Figure also shows correlation of cal drivers of chronic heart failure (CHF) acting via V1a-, V1b- and V2 wall thickness with contractility (scatter plots, < i > n < /i > = 4–7 per receptors. Selective V2 and dual V1a-V2 receptor antagonists amelio- group; symbols represent individual aortas). The stronger an individ- rate plasma sodium levels, but fail to reduce mortality in clinical stud- ual aorta was able to contract (larger absolute stress change; to the ies. Vasopressin neutralization is an original alterative for receptor left on < i > x < /i > -axis), the weaker its remodelling response. blockers but its effect in CHF is unknown. For this purpose, we sought Conclusions: NE- and AngII-induced hypertension elicit distinct investigated the short-term cardiac and vascular effects of the vaso - aortic remodelling responses. However, independent of the hyper- pressin neutralizing aptamer NOX-F37. tensive stimulus, aortic contractile capacity emerged as protective Methods: Left ventricular (LV) function (hemodynamics by LV cath- against hypertensive arterial remodelling. erization) and LV tissue perfusion (MRI) as well as mesenteric artery endothelium function (flow mediated dilation by arteriograph) were determined 2 h after NOX-F37 administration (80 nM/kg; IP) to rats with well-established CHF induced by coronary artery ligation. Results: Two hours after administration, NOX-F37 significantly improved LV systolic function, illustrated by the significant increase in LV end-systolic pressure volume relation (CHF: 20.2 ± 0.0.7; CHF + NOX: 23.3 ± 1.0 mmHg/RVU) and diastolic function, illustrated by the sig- nificant decrease in LV end-diastolic pressure volume relation (CHF: 4.03 ± 0.48; CHF + NOX: 2.06 ± 0.21 mmHg/RVU), which were associ- ated with a significant increase in LV tissue perfusion (CHF: 6.12 ± 0.24; CHF + NOX: 10.10 ± 0.26 ml/min/g LV tissue). However, mesenteric artery flow-induced dilatation was not modified and remained impaired (% dilatation at 150 µl/min; CHF: 10 ± 7; CHF + NOX: 9 ± 8). Conclusions: These results illustrate the immediate protective effects on cardiovascular function of vasopressin neutralization in chronic heart failure confirming the existence of a deleterious vaso - pressinergic tone in chronic heart failure. Whether these beneficial cardiac effects persist with chronic vasopressin neutralization needs to be confirmed. Keywords: Heart failure; pharmacology; vasopressin O.27 Hypertensive aortic remodelling as induced by adrenergic receptor activation vrsus renin–angiotensin–aldosterone system activation in mice 1,2,3 2 2 Bart Spronck , Alexander W. Caulk , Abhay B. Ramachandra , Sae‑Il 2 2,4 Murtada , Jay D. Humphrey Dept. of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands, Dept. of Biomedical Engineering, Yale University, New Haven, United States, Macquarie Medical School, Macquarie University, Sydney, Australia, Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, United States Background: Hypertension causes the aorta to remodel and poten- tially stiffen. We aimed to compare the aortic remodelling response to hypertension as induced by adrenergic receptor activation versus renin–angiotensin–aldosterone system activation. Methods: Adult male C57BL/6 J mice were studied under seven con- ditions: untreated, and after 7/14/28-day subcutaneous infusion of 3880 ng/kg/min norepinephrine (NE) or 1000 ng/kg/min angioten- sin II (AngII). After euthanasia, ascending/descending thoracic (ATA/ Whiskers: standard errors, overbars: < i > p < /i > < 0.05 (Bonferroni). Sys- DTA) and infrarenal abdominal (IAA) aortas were dissected, placed tolic/diastolic blood pressures: 120/80 mmHg (WT); 154/103, 162/108, within a computer-controlled biaxial testing device, and subjected 154/103 mmHg (7/14/28d NE); 150/100, 159/106, 177/118 mmHg to isobaric (90 mmHg) vasoreactivity experiments to, among others, (7/14/28d AngII). Lines/grey areas: multilevel regressions/95% confi- 1 µM phenylephrine + 1 mM L-NAME [1]. Under passive conditions, dence intervals. A rtery Research References Basic [1] Spronck B, Latorre M, Wang M, Mehta S, Caulk AW, Ren P, et al. Excessive adventitial stress drives inflammation‑mediated fibrosis in hyperten‑ P.001 sive aortic remodelling in mice. J R Soc Interface 2021; 18:20,210,336. Variability of invasive aortic pulse wave velocity measured [2] Owens AP, 3rd, Subramanian V, Moorleghen JJ, Guo Z, McNamara CA, Cassis by catheter pull‑back method and implications for pulse wave LA, Daugherty A. Angiotensin II induces a region‑specific hyperplasia of velocity device validation the ascending aorta through regulation of inhibitor of differentiation 3. 1 2,7 2,8 Alexander Stäuber , Bart Spronck , Alessandro Giudici , Cornelia Circ Res 2010; 106:611–619. 3 3 4 5 Piper , Siegfried Eckert , Stefan Richter , Marc‑Alexander Ohlow , Johannes Baulmann Keywords: Angiotensin II; arterial mechanics; norepinephrine; vasoconstriction Professorship of Sports Medicine / Sports Biology, Chemnitz University of Technology, Chemnitz, Germany, Department of Biomedical Engineer‑ O.28 ing, CARIM School for Cardiovascular Diseases, Maastricht University, Raised arterial stiffness at 24–26 weeks of gestation is associated Maastricht, The Netherlands, Klinik für Allgemeine und Interventionelle with the development of hypertension in pregnancy Kardiologie/Angiologie, Herz‑ und Diabeteszentrum NRW, Univer ‑ sitätsklink der Ruhr‑Universität Bochum, Bad Oeynhausen, Germany, 1 1 1 1 Pritika Dutta, Tarang Gupta , Rajesh Kumari, Vidushi Kulshrestha , Department of Cardiology, Zentralklinik Bad Berka GmbH, Herzzentrum, 1 1 1 Ashok Kumar Jaryal , Kishore Kumar Deepak , Garima Kachhawa. Department of Cardiology, Bad Berka, Germany, Department of Cardiol‑ 1 6 All India Institute of Medical Sciences, New Delhi, India ogy, SRH Wald‑Klinikum, Gera, Germany, Praxis Dres. Gille/Baulmann, Rheinbach, Germany, Macquarie Medical School, Faculty of Medicine, Background: Increase in arterial stiffness in third trimester is pro - 8 Health and Human Sciences, Macquarie University, Australia, GROW posed to be involved in the pathogenesis of hypertensive disorders School for Oncology and Reproduction, Maastricht, The Netherlands of pregnancy. The present study was conducted to evaluate arte- rial stiffness in pregnant women at 24–26 + 6 weeks of gestation. Background: The invasive method of catheter pullback from ascending They were grouped into healthy pregnancy (HP), preeclampsia aorta (asc) to iliac bifurcation (bifu) is gold standard for aortic pulse wave (PE) or gestational hypertension (GHTN) depending upon maternal velocity (aPWV) and the reference standard for validation of non-invasive outcome. devices that estimate aPWV [1]. In this work, we examine aPWV variability Methods: Arterial stiffness was measured using applanation tonom- in invasive recordings of patients undergoing cardiac catheterization. etry. Central arterial stiffness was quantified by augmentation index Methods: Invasive measurements were performed in 56 patients (57% normalized to heart rate 75 beats/minutes (AIx@75) and carotid- male, 67 ± 13 years, mean ± standard deviation (SD)) with a femoral femoral pulse wave velocity (cfPWV), peripheral arterial stiffness catheter access. Catheter pullback method was used to measure aortic was quantified by carotid-radial pulse wave velocity (crPWV) using pulse transit time (aPTT ) from asc to bifu. Pulse wave analysis using the SphgmoCor CVMS CPVH device. intersecting tangent method (Sirius, Redwave Medical GmbH, Jena, Results: Out of 313 women, PE developed in 3.51% (n = 11), GHTN Germany) provided the diastolic foot points for each recording site in 5.11% (n = 16) and 22.04% (n = 69) remained healthy preg- (asc, bifu) and recorded heartbeat (number of beats, asc: 86 ± 42, bifu: nant without any obstetrical or medical factors. The mean age in 82 ± 43). From the respective time difference with the R-wave of the years, BMI in kilograms/metre2 and MAP in mmHg between the time-synchronised electrocardiogram, the pulse transit time for the groups were [(30.0 ± 1.6 vs 28.81 ± 4.8 vs 27.70 ± 4.0, p = 0.094), corresponding recording site (PTTasc, PTTbifu) was derived for each {27.41(25.10–33.09) vs 28.51(24.29–31.84) vs 27.01(25.39–28.40), heartbeat. aPTT was then determined from the difference of the aver - p = 0.529}, (99.09 ± 7.58 vs 95.88 ± 9.09 vs 85.99 ± 9.64, p < 0.0001)] aged PTTbifu and PTTasc. Based on aPTT, the known catheter pullback respectively. AIx@75 was found to be increased (PE:22.82 ± 14.65%, length and the estimated SD of aPTT, SD_aPTT = √(SD_PTTasc + SD_ GHTN:19.47 ± 10.60%, HP:10.35 ± 12.14%, p = 0.001) in women devel- PTTbifu ), the SD of the corresponding aPWV was calculated as SD_ oping hypertension in pregnancy than normotensive healthy preg- aPWV = aPWV × SD_aPTT/aPTT for each patient. nancy. Similarly cfPWV (PE:7.21 ± 1.24 m/s, GHTN:6.64 ± 1.22 m/s, HP: Results: aPTT was 44.01 ± 12.89 ms; aPWV was 9.7 ± 3.1 m/s. SD_aPT T 6.19 ± 1.06 m/s, p = 0.013) was also significantly higher in pregnant was 3.72 ± 1.73 ms, resulting in an SD_aPWV of 1.0 ± 0.8 m/s. women with PE and GHTN. The crPWV were comparable among PE, Conclusions: Our data indicate a substantial beat-to-beat SD in inva- GHTN and healthy pregnant. sively determined aPWV by catheter pull-back method. The issue of Conclusion: Raised central arterial stiffness is observed before the aPWV variability in the invasive reference needs to be addressed in clinical onset of disease in women destined to develop PE later in validation protocols for non-invasive estimation of aPWV. pregnancy. AIx@75 and cfPWV could be used as a putative prognos- tic marker of hypertensive disorders of pregnancy. Reference [1] Wilkinson IB, McEniery CM, Schillaci G, Boutouyrie P, Segers P, Donald A, References Chowienczyk PJ (2010). ARTERY Society guidelines for validation of non‑ 1.Garg P, Jaryal AK, Kachhawa G, Kriplani A, Deepak KK. Sequential profile of invasive haemodynamic measurement devices: Part 1, arterial pulse wave endothelial functions and arterial stiffness in preeclampsia during the velocity. Artery Research, 4(2), 34–40. course of pregnancy. Pregnancy Hypertens. 2019; 18: 88–95. 2.Franzi MB, Burgmann M, Neubauer A, Zeisleri H, Sanani R, Gottsauner‑ Wolf Keywords: PWV, PTT, variability M et al. Augmentation index and pulse wave velocity in normotensive and pre‑ eclamptic pregnancies. Acta. Obstet. Gynecol. Scand. 2013; 92: 960–66. P.002 3. Tomiyama H, Yamashina A. Non‑invasive vascular function tests: Their patho ‑ Multiple linear regression analysis of age, gender, anthropometric physiological background and clinical application. Circ. J. 2010; 74: 24–33. and haemodynamic factors to predict variability in aortic pulse transit time determined by the catheter pull‑back method Keywords: Arterial stiffness, augmentation index, pulse wave velocity, 1 2,7 2,8 Alexander Stäuber , Bart Spronck , Alessandro Giudici , Cornelia hypertensive disorders of pregnancy 3 3 4 5 Piper , Siegfried Eckert , Stefan Richter , Marc‑Alexander Ohlow , Posters Johannes Baulmann. Artery Research Professorship of Sports Medicine/Sports Biology, Chemnitz University mice survival. qPCR analysis indicated the altered expression of cir- of Technology, Chemnitz, Germany, Department of Biomedical Engineer‑ cadian-related genes such as genes of Bmal and ciart. ing, CARIM School for Cardiovascular Diseases, Maastricht University, Conclusions: Our data indicate the primary effect of Bcl11b inacti- Maastricht, The Netherlands, Klinik für Allgemeine und Interventionelle vation on cell death, probably by necroptosis. Kardiologie/Angiologie, Herz‑ und Diabeteszentrum NRW, Univer ‑ sitätsklink der Ruhr‑Universität Bochum, Bad Oeynhausen, Germany, Department of Cardiology, Zentralklinik Bad Berka GmbH, Herzzentrum, Department of Cardiology, Bad Berka, Germany, Department of Cardiol‑ ogy, SRH Wald‑Klinikum, Gera, Germany, Praxis Dres. Gille/Baulmann, Rheinbach, Germany, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Australia, GROW School for Oncology and Reproduction, Maastricht, The Netherlands Background: Aortic pulse transit time (aPTT) is not constant but fluc - tuates, which affects the accurate determination of aortic pulse wave velocity (aPWV). In this work, we investigate the influence of age, gen- der, anthropometric and haemodynamic parameters on aPTT variabil- ity determined by the catheter pull-back method. Methods: aPTT could be analysed in 69 patients (61% male, 68 ± 13 years) with femoral catheter access. A stepwise multiple linear regression analysis was performed with aPTT variability as dependent variable and age, gender, BMI, heart rate, aortic systolic blood pressure (aSBP), aortic diastolic blood pressure (aDBP) and variability of aSBP (aSBPV ) and aDBP (aDBPV ) as predictors. For the dependent haemody- namic variables, only data from the ascending aorta were used. Results: The regression model with the factors heart rate, aSBP, aSBPV, aDBPV achieved the highest goodness of fit of 0.49 (adjusted R-squared). aSBPV and heart rate proved to be the strongest factors (standardised regression coefficient beta 0.397 and 0.301, respec - tively) followed by 0.258 for aDBPV and -0.199 for aSBP (all p < 0.05). Photos showing thoracic aorta from control (A) and mutant mice (B) at The unstandardised regression coefficients B were 0.489 for aSBPV, 7 days after the injection of tamoxifen to 3 month-old mice. 0.322 for aDBPV, -0.020 for aSBP and 0.047 for heart rate. Conclusions: Our data show the influence of aortic systolic and diastolic References blood pressure variations, heart rate and aSBP on aPTT variability whereas Mitchell GF, Verwoert GC, Tarasov KV et al., Common genetic variation in the age, gender, and BMI had no significant influence. However, the adjusted 3’‑BCL11B gene desert is associated with carotid‑femoral pulse wave R-squared of the model suggests that a considerable part of aPTT variability velocity and excess cardiovascular disease risk: the AortaGen Consortium. cannot be explained by the independent variables included in the model. Circ Cardiovasc Genet. 2012;5(1):81–90. Valisno JAC, May J, Singh K, Helm EY, Venegas L, Budbazar E, Goodman JB, Keywords: PTT variability, PWV variability Nicholson CJ, Avram D, Cohen RA, Mitchell GF, Morgan KG, Seta F. BCL11B Regulates Arterial Stiffness and Related Target Organ Damage. Circ Res. 2021;128(6):755–768. P.003 Keywords: Cell death, CTIP2/Bcl11b, hemorrhage Smooth muscle cell‑specific knock‑out of CTIP2 gene results in aortic hemorrhage 1,2,3 1,2,3 1,2,3 P.004 Ara Parlakian , Jocelyne Blanc , Jacqueline GAO‑Li , Véronique 4 1,2,3 4 1,2,3 Smooth muscle integrin αv contributes to the regulation of cell Regnault , Onnik A gbulut , Patrick Lacolle y , Zhenlin Li stiffness 1 2 Sorbonne Universite, Paris, France, CNRS UMR8256, Paris, France, 1 2 3 3 4Alexandre Raoul , Ekaterina Belozertseva, Lei Tian , Xiao Liu , INSERM ERL U1164, Paris, France, INSERM—U1116, Nancy, France 3 2 2 4 Caterina Maria Tone , Jocelyne Blanc , Dario Coletti , Daniel Henrion , 1 1 3 Background: Ctip2/Bcl11b is a transcription factor with dual action Véronique Regnault , Patrick Lacolley , Emmanuelle Lacaze , Pascal 5 2 (repression/activation) that couples epigenetic regulation to gene Challande , Dr Zhenlin Li transcription in a variety of physiological responses under healthy 1 2 INSERM1116, Vandoeuvre‑lès‑nancy, France, CNRS8256, Paris, France, and pathological conditions of various tissues. Single nucleotide 3 4 CNRS7588, Paris, France, INSERM1083 – CNRS6214, Angers, France, polymorphisms of Ctip2/Bcl11b gene are associated with a higher CNRS7190, Paris, France susceptibility for aortic stiffness (1). although Ctip2/Bcl11b has been proposed as a crucial regulator of aortic smooth muscle func- Background: Integrin αv is a receptor for adhesion proteins expressed tion (2), its mechanism of action in smooth muscle cells is still to be at high density in vascular smooth muscle cells (VSMC) whose pheno- uncovered. typic modulation plays a crucial role in arterial ageing. Methods: Morphological, cellular and molecular analysis were car- Objectives: To define the arterial phenotype in mice conditionally ried out on the arteries of smooth muscle cell-specific Ctip2-knock - inactivated for the integrin αv subunit in VSMC and the role of this out (KO) mice at 3, 7, 28 days after tamoxifen injections. integrin in angiotensin II (Ang II)-induced arterial and VSMC stiffness. Results: There is no difference between control and mutant mice Methods and results: We used a VSMC specific knock-out αv mouse at the macroscopic level 3 days after Ctip2 KO induction, however, model induced in adult mice by injection of tamoxifen. Trangenic 7 day after Bcl11b inactivation, 65% of the Ctip2-SMKO mice showed mice (αvSMKO) and control littermates (Ctrl) were infused with Ang II signs of hemorrhage in the distal part of the thoracic aorta near the (1.5 mg/kg/day) for 4 weeks. The pressure effect of Ang II was similar in abdominal aorta. The histological examination of thoracic aorta at 7 Ctrl and αvSMKO mice. The carotid distensibility/pressure and elastic indicated the presence of “bumpy region” in the mutant aorta. These modulus/wall stress curves were similar in control and αvSMKO mice, areas is covered by a thicker layer of extracellular matrix and the indicating comparable arterial stiffness. Ang II treatment resulted in presence of IgG positive cells, indicating that cell death is occurring. increased carotid stiffness in both groups without changes in vascu- However, the hemorrhages is contained over time, do not impact lar reactivity and myogenic tone. Electronic microscopy revealed less A rtery Research vesicles containing fiber-like materials in the SMCs of Ang II-treated cardiovascular pathologies [2]. In the current project, we explore the αvSMKO carotids Elastic modulus of cultured VSMCs determined using impact of an AT biased agonist (TRV027) on the regulation of the cer- atomic force microscopy was higher after Ang II treatment in cells from ebral circulation. both groups. At baseline and after treatment, elastic modulus was Methods: We evaluated the TRV027 signaling on HEK293-cells higher in cells from αvSMKO mice than in cells from Ctrl mice.overexpressing AT using bioluminescence resonance energy Conclusion: Inactivation of αv-containing integrins on VSMCs transfer (NanoBRET) and calcium mobilization assays. In parallel, con- increases cell stiffness. The general mechanism involves a cross-talk centration–response curves to TRV027 were built on an ex vivo model between extracellular matrix, αv integrins and cytoskeletal complex. of isolated and perfused middle cerebral arteries (MCA) by measuring The lack of distensibility changes suggests additional changes at the changes in internal diameter. level of αv-mediated dynamics of focal adhesion. Results: BRET results show that TRV027 induces an activation of the β-arrestin pathway with a maximal increase of BRET ratio of 0.08 while Keywords: Integrin αv, vascular smooth muscle cells, cell stiffness inactivating the Gq pathway. Calcium mobilization assays confirm this Gq inactivation. As expected, results obtained in MCA show no effect of TRV027 on arterial diameter. P.005 Discussion: Tracking the A T receptor using specific fluorescent tools Estrogen modulates phenotypic state of male vascular smooth to follow its internalization (confocal microscopy) is currently under muscle cells exposed to flow conditions development. 1 1 1 1 The next step will be to assess in vivo the potential beneficial and pro - Enzo Lecoq , Nathan Wisniewski , Leo Jannot , Eva Feigerlova tective effects of TRV027 in cerebrovascular pathologies, in collabora- INSERM UMR_S 1116—DCAC Université de Lorraine, Nancy, France tion with Maastricht University. Although an estrogen-mediated vasculoprotective effect is widely References accepted in premenopausal women, literature data indicate that 1. Violin JD, Lefkowitz RJ. β‑Arrestin‑biased ligands at seven‑transmembrane estrogen therapy in transgender women confer an increased risk of receptors. Trends Pharmacol Sci. août 2007;28(8):416‑22. cardiovascular events. Vascular smooth muscle cell (VSMC) reside in a 2. Boerrigter G, Soergel DG, Lark MW, Burnett JC. TRV120027, a Novel Beta‑ 3-dimensional environment and are not normally exposed directly to Arrestin Biased Ligand at the Angiotensin II Type I Receptor, Unloads the shear stresses of flowing blood in the vascular system, because the the Heart and Maintains Renal Function When Added to Furosemide in endothelial cell layer provides the contacting surface for blood flow. Experimental Heart Failure. J Card Fail. août 2011;17(8):S63‑4. However, in cases of endothelial injury, the superficial layer of SMCs is exposed directly to blood flow shear stresses. We hypothesized that Keywords: AT receptor; cerebral circulation; β-arrestin; biased agonist treatment of male VSMCs with estrogens alters cell behavior. Our aim was to study the effect of shear stress on male VSMCs in a 2D Imaging technologies environment under flow model. Cells were treated with 17-β-estradiol and cultured in the Ibidi chamber under laminar flow and shear stress −2 of 1–2 dyn.cm . The cell orientation and morphology and phenotypic P.011 changes were analyzed. Non‑contact Method for Fast Localization of Perforator Arteries Results: We observed an increased expression of MYH10 exposed to 1,2 1 3,4 Valentina Vassilenko , Anna Poplavska , Diogo Casal , Edivaldo shear stress. The expression of MYH10 seems to be correlated with the 1,4 Junior orientation of VSMCs. The orientation of VSMCs treated with estrogens is parallel to the culture medium flow. Our preliminary results further Nova School Of Science And Technology—Nova University Of Lisbon, suggest an increased expression of the MMP-2 under estrogen treat- Campus FCT UNL, Portugal, Iberian Network on Arterial Structure, ment under flow conditions in the 2D model. Central Hemodynamics and Neurocognition,, Portugal, Plastic Conclusion: The differential effects of laminar flow and shear stress and Reconstructive Surgery Department and Burn Unit, Centro Hospitalar flow may be due to the different phenotypic state of the VSMCs. de Lisboa Central, Lisbon, Portugal, Anatomy Department, Nova Medical School—Nova University of Lisbon, Lisbon, Portugal Keywords: Sex hormones, Laminar flow and shear stress flow, Vascular Recently an extensive clinical experience in flap surgery has con- smooth muscle cell firmed that its success depends on the correct identification of vital perforator vessels [1]. Unfortunately, the perforator vessels frequently have a variable location. So, the knowledge about perforator anatomy Brain during preoperative planning is one of the most critical factors. In this work, we present the method and experimental results for non- P.006 contact and fast localization of the cutaneous perforators using Infra- Physiological effects of a biased angiotensin II type 1 receptor red Thermography (IRT ). This imaging technique can provide real-time agonist on cerebral circulation information on skin perfusion by measuring body surface tempera- 1,4 1 2 3 Mélissa Colin , Céline D elaitre , Sandra L ecat , Samir Acherar , ture. Validation of the method was performed against the ultrasound 4 1 1 Sébastien Foulquier , Isabelle Lartaud , François Dupuis. technology realized in the hand-held Doppler flowmeter, which is 1 2 widely used in most hospitals and is an essential tool where a rapid Université de Lorraine, CITHEFOR, Vandoeuvre‑lès‑Nancy, France, Uni‑ analysis of the vascular status of a patient is routine. versité de Strasbourg, CNRS, Biotechnologie et Signalisation Cellulaire, 3 Both technics were applied in this work for the identification of forearm Illkirch‑Graffenstaden, France, Université de Lorraine, CNRS, LCPM, Nancy, 4 cutaneous perforator vessels. The reflection of sound waves, predomi- France, Maastricht University, School for Mental Health and Neurosci‑ nantly from intravascular blood flow of the forearm, was registered by a ence, Maastricht, The Netherlands hand-held BT-200 V Vascular Doppler pan. The infrared images were Background: The angiotensin II type 1 (AT ) receptor has a relevant obtained by two cameras: FLIR E6 with temperature sensitivity < 0.06 °C role in the physiology and pathophysiology of the cerebrovascular and (320 × 240)-pixel display resolution, and Thermal Expert with sensitiv- system. Its vasoconstrictor effect, consecutive to Gq protein activa- ity < 0.05 °C and array format 640 × 480. Perforator mapping of the fore- tion, reduces cerebral perfusion during stroke. In addition, A T recep- arm area ware compared for accuracy, timing, and the operator’s skills. tor activity is directly regulated by the β-arrestin pathway, involved Obtained results show that IRT images provide valuable real-time in receptor internalization [1]. Recently, the development of biased information on the hemodynamic quality of perforators and their agonists, able to selectively activate the β-arrestin pathway without accurate location. Its potential to reveal underlying perforator vessels Gq activation appears to be a promising new therapeutic strategy in may also be used for postoperative monitoring of flap perfusion [2]. Artery Research References Methods: 49 runners (A) trained for 8.5 ± 8.9 years, 3.9 ± 1.4 days/ [1] D. Casal et al., “A Model of Free Tissue Transfer: The Rat Epigastric Free Flap,” week and 15 sedentary (S) subjects matched by sex, age, BMI, baseline J. Vis. Exp., no. 119, pp. 14–16, 2017. brachial pressures and heart rate underwent ultrasound semi-auto- [2] T. Sjøberg, J. B. Mercer, S. Weum, and L. de Weerd, “The Value of Dynamic matic assessment of the vascular system (arterial mean diameters, MD, Infrared Thermography in Pedicled Thoracodorsal Artery Perforator Flap and distensibility, DC, of abdominal aorta, common carotid, common Surgery,” Plast. Reconstr. Surg. – Glob. Open, vol. 8, no. 7, 2020. femoral, brachial artery) and of cardiac parameters. Central pressure- based (applanation tonometry) hemodynamic properties according to Keywords: Cutaneous Perforator Vessels (CPVs), Infrared Thermogra- the reservoir theory were derived. phy (IRT ), hand-held Doppler devices (HHDD), perforator mapping Results: Cardiac parameters related to dimensions, mass and vol- umes showed significantly higher values in A compared to S (A/S: Left Ventricular Internal diameter, 29 ± 3 mm/27 ± 3 mm; Left Ventricular P.013 Mass, 161 ± 31 g/141 ± 25 g; Aortic root size 30 ± 3 mm/27 ± 2 mm; Radial artery phenotyping in systemic sclerosis Stroke Volume, 76 ± 13 mL/69 ± 16 mL; Arterial Elastance, 7 ± 1 mm through ultra‑high frequency ultrasound: a radiomic approach –1 –1 HgmL /6 ± 1 mm HgmL ). 1 2 3 1,3 Federica Poli , Goncalo Boleto , Hakim Khettab , Pierre Bout ouyrie , MD was greater in each large arterial site in A than in S reporting a 2 1,3 Yannick Allanore , Rosa Maria Bruno trend in the carotid and significant differences in aorta and femoral artery (aorta: 16 ± 2 mm/13 ± 1 mm; femoral: 10 ± 1 mm/9 ± 1 mm). Paris Cardiovascular Research Center (PARCC)‑INSERM UMR‑970, Paris, DC evidenced a lowering trend in A for each arterial site except for the France, Department of Rheumatology, Université de Paris, Cochin Hospi‑ brachial artery. Hemodynamic parameters showed higher reservoir tal, Paris, France, AP‑HP, Hopital Européen Georges Pompidou, Université pressure in A compared to S (Pressure reservoir integral, 14 ± 4/11 ± 3). de Paris, Paris, France Conclusions: Strenuous exercise induced a well-known cardiac Background: Systemic sclerosis (SSc) is a disorder characterized by a remodeling which can be hypothesized to be slower in the arte- massive vascular involvement. Imaging biomarkers of vascular involve- rial tree because of highly differentiated and complex mechanism ment in SSc may have potential clinical implications for prediction of aiming to heart protection. Accordingly, the increased reservoir the pathogenesis of vascular complications [1]. This study is aimed at pressure in runners could be interpreted as sentinel parameter of identifying possible patterns of vascular wall disarray and remodeling vascular “fatigue”. in radial arteries of SSc patients, by means of ultrahigh frequency ultra- sound (UHFUS). References Methods: 5 end-diastolic frames of the right radial arteries of 41 1. Heffernan KS, Yoon ES, Sharman JE, Davies JE, Shih Y T, Chen CH, et al. patients with SSc and 41 healthy controls were obtained by VevoMD Resistance exercise training reduces arterial reservoir pressure in (70 MHz probe, FUJIFILM, VisualSonics, Toronto, Canada). 74 radiomic older adults with prehypertension and hypertension. Hypertens Res. features and 4 engineered parameters were extracted: inner and outer 2013;36(5):422–7. layer thickness, and presence of adjunctive acoustic interfaces (triple 2. Ramos JS, Ramos M V., Dalleck LC, Borrani F, Walker KB, Fassett RG, et al. signal). A feature selection algorithm was applied to reduce the num- Fitness Is Independently Associated with Central Hemodynamics in ber of features. The selected features were used to train classification Metabolic Syndrome. Med Sci Sports Exerc. 2016;48(8):1539–47. model, using Linear Support Vector Machine (SVM). 3. Ujka K, Bruno RM, Bastiani L, Bernardi E, Sdringola P, Dikic N, et al. Results: The SVM classification model showed good performance Relationship between occupational physical activity and subclinical (sensitivity = 0.63, specificity = 0.88, accuracy = 0.75, AUC = 0.75) to vascular damage in moderate‑altitude dwellers. High Alt Med Biol. discriminate SSc patients from controls using sixteen selected fea- 2017;18(3):249–57. tures. Inner layer (208 ± 61 vs 179 ± 47 µm, p = 0.04) and outer layer thickness (104 ± 22 vs 120 ± 36 µm, p = 0.03) were significantly higher Keywords: Cardiovascular adaptation, exercise, ultrasound in SSc than in controls, triple signal pattern more frequent in patients (p = 0.002). Conclusions: Wall ultrastructure of radial arteries of SSc patients is P.015 altered: inner and outer layer thickened, showing frequently a triple Sex‑related differences in skin microvascular function of healthy signal pattern. Radiomic approach allow to distinguish between radial normotensive individuals as assessed with laser speckle contrast images from SSc patients and controls with a 75% accuracy. imaging 1 1 1 Reference Antonios Lazaridis , Konstantinos Mastrogiannis , Anastasia Malliora , 1 1 1 1. Allanore Y, Distler O, Matucci‑ Cerinic M, Denton CP. Review: Defining a Stamatina Lamprou , Nikolaos Koletsos , Barbara Nikolaidou , Panagiotis 1 1 1 Unified Vascular Phenotype in Systemic Sclerosis. Arthritis Rheumatol Dolgyras, Areti Triantafyllou , Eugenia Gkaliagkousi Hoboken NJ. febbraio 2018;70(2):162–70. 3rd Department of Internal Medicine, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Keywords: UHFUS, radial arteries, radiomic analysis, machine learning Background: Skin microcirculation is considered a window to assess generalized microvascular function. Changes in skin micro- P.014 Cardiovascular adaptation to strenuous exercise: exploring vascular function (SMF) have been identified in several cardiovas- the complexity of the arterial protective role for the heart cular disease states. However, scarce data exists regarding SMF in 1 1 1 Maria Raffaella Martina , Elisabetta Bianchini , Marco Scalese , Nicole healthy adults and the impact of gender on it [1,2]. In this study, we 1 2 1 Di Lascio , Rosa Maria Bruno , Lorenza Pratali. assessed SMF in healthy individuals with the dynamic technique Lase Speckle Contrast Imaging (LSCI). Institute of Clinical Physiology—Italian National Research Council Methods: Healthy normotensives were included in the study. Office (CNR‑IFC), Pisa, Italy, Université Paris Cité, Inserm, PARCC, F‑75015, Paris, blood pressure (BP) was measured according to standard guidelines. France SMF was assessed with LSCI (PeriCam PSI NR, Perimed, Sweden) cou- pled with post-occlusive reactive hyperemia (PORH). Results were Background: The intense exercise effect evaluation on the cardiovas- expressed as perfusion during baseline, occlusion and peak period cular system can help to profile and reduce the risks (1–3). This work (arbitrary Perfusion Units,PUs), time until maximal perfusion (sec), the aims at assessing cardiovascular adaptation in runners by a multi-site percentage increase of perfusion between baseline and peak period non-invasive approach. A rtery Research (%) and PORH amplitude calculated as peak cutaneous vascular con- ductance (CVC) – baseline CVC. CVC was calculated as mean perfu- sion during each PORH period divided by mean BP (LSPUs/mmHg). Results: We studied 86 healthy normotensives including 50 women and 36 age-matched men. Body mass index, creatinine, office sys- tolic BP (SBP) and diastolic BP (DBP) were significantly higher in men compared to women. Regarding SMF, perfusion during baseline and occlusion, baseline CVC, peak CVC and PORH amplitude (0.89 ± 0.21 vs 0.75 ± 0.19, p < 0.01) were significantly higher in females compared to males. In addition, PORH was negatively associated with office SBP (r = − 0.258, p < 0.05). Conclusions: Healthy females present significantly higher SMF param- eters compared to age-matched males. Further research is needed to clarify the impact of gender on microvascular function and its further implications. References (a): AA longitudinal (white) and radial (red) strain from sagittal MRI [1] Stupin A, Stupin M, Baric L, Matic A, Kolar L and Drenjancevic I. Sex‑related (b): Dist-axial (left), DistR-sagittal (middle) and DistL-sagittal (right) differences in forearm skin microvascular reactivity of young healthy according to subject group: HV < 40 years, HV ≥ 40 years and AVS subjects. Clin Hemorheol Microcirc. 2019;72(4):339–351. patients. [2] Hodges G, Sharp L, Clements R, Goldspink R, George K, and Cable N. Influ‑ ence of age, sex, and aerobic capacity on forearm and skin blood flow References and vascular conductance. Eur J Appl Physiol. 2010;109(6):1009–15. [1] Lamy J, Soulat G, Evin M, Huber A, de Cesare A, Giron A, et al. Scan‑rescan reproducibility of ventricular and atrial MRI feature tracking strain. Com‑ Keywords: Microcirculation, laser speckle contrast imaging, perfusion, put Biol Med. 2018; 92:197–203. https:// doi. org/ 10. 1016/j. compb iomed. skin microvascular function 2017. 11. 015. [2] Redheuil A, Yu WC, Wu CO, Mousseaux E, de Cesare A, Yan R, Kachenoura P.021 N, Bluemke D, Lima JA. Reduced ascending aortic strain and distensibil‑ Longitudinal and radial distensibility of the ascending aorta ity: earliest manifestations of vascular aging in humans. Hypertension. in aging and aortic valve stenosis using MRI feature tracking 2010 Feb;55(2):319–26. https:// doi. org/ 10. 1161/ HYPER TENSI ONAHA. 109. 1,2 3 1 141275. Marie Shannon Soulez , Jérôme Lam y, Vincent Nguyen , Umit 4 4 4 1 Gencer , Gilles Soulat , Elie Mousseaux , Emilie Bollache , Nadjia 1 Keywords: MRI, Aortic strain, Aging, Aortic valve stenosis Kachenoura Sorbonne Université, CNRS, INSERM, Laboratoire d’Imagerie Biomédicale, Hypertension 2 3 LIB, Paris, France, Université Paris‑Est Créteil, Creteil, France, Department of Radiology and Biomedical Imaging, Yale University, New Haven, USA, P.022 PARCC, Université de Paris, Inserm/AP‑HP, Hôpital Européen Georges Exploring strain‑dependent collagen degradation as a driver Pompidou, Paris, France of hypertension‑induced arterial remodelling in lean ZSF1 rats: Background: We aimed to test the feasibility of MRI-based feature a pilot study tracking (FT) to measure longitudinal strain and radial motion frac- 1,2 1,2 3,4 Koen van der Laan , Koen Reesink , Sara Lambrichts , Laura van der tion of the proximal ascending aorta (AA) and to investigate how these 1,3 1 1,2 1,3,4 Taelen , Nicole Bitsch, Tammo Delhaas , Sebastien Foulquier , Bart measures are affected by aging and by the presence of calcified aortic 1,2,5 Spronck valve stenosis (AVS). 1 2 Methods: Twenty healthy volunteers (HV ) < 40 years (29 ± 1.6 years, 10 Carim, University Maastricht, Maastricht, Netherlands, Department males), 20 HV ≥ 40 years (58 ± 1.5 years, 10 males) and 31 patients with of Biomedical Engineering, Maastricht University medical centre, AVS (73 ± 1.6 years, 20 males) underwent 2D cine thoracic aortic MRI in Maastricht, Netherlands, Department of Pharmacology & Toxicology, sagittal and axial views immediately followed by carotid artery appla- Maastricht University, Maastricht, Netherlands, MHENS School for Mental nation tonometry. AA anterior wall (Figure a) was semi-automatically Health and Neuroscience, Maastricht University, Maastricht, Netherlands, tracked on sagittal images throughout the cardiac cycle to estimate Macquarie Medical School, Faculty of Medicine, Health and Human Sci‑ longitudinal strain and radial motion fraction peaks, while using cus- ences, Macquarie University, Sydney, Australia. tom FT software [1], which was previously dedicated to multi-chamber Background: Hypertension-induced arterial remodelling involves e.g., strain evaluation in the heart. Conventional global AA strain was also increased wall thickness, changes in collagen structure and increased measured on axial views based on cross-sectional area [2]. Finally, dis- collagen content [1]. Normally, collagen is degraded and deposited in tensibility was derived as strain/central pulse pressure. 8–10 week turn-over cycles [2]. Collagen fibre strain significantly influ- Results: Axial (Dist-axial: R = − 0.82, p < 0.0001) and sagittal (radial ences enzymatic degradation efficiency, where straightened but not DistR-sagittal: R = − 0.54, p = 0.0004, longitudinal DistL-sagittal: overstretched fibres experience minimum degradation (Fig. A) [3]. In R = − 0.37, p = 0.02) distensibility measures decreased significantly a homeostatic situation where collagen experiences minimum deg- with age and even more in the presence of AVS (Figure b). When inves- radation at mean arterial pressure, fibres would be optimally strained tigating the ability of distensibility measures to discriminate HV from [4]. The onset of hypertension overstretches collagen (1 in Fig. B), patients, newly proposed DistR-sagittal (0.84) and DistL-sagittal (0.92) demonstrated higher area under the ROC curve than Dist-axial (0.81). Conclusions: MRI FT revealed that age has a stronger impact on AA axial distensibility, while longitudinal distensibility could be more sen- sitive to the effect of AVS probably because of valvular calcifications that limit this longitudinal motion specifically. Artery Research accelerating collagen degradation [4]. We hypothesise that optimally P.024 strained fibres will gradually make up the bulk of collagen during Eec ff ts of Nitroglycerin Induced Vasodilation on Elastic hypertension, as overstrained collagen degrades faster. This implies versus Muscular Artery Stiffness in Older Veterans that, as collagen returns to the optimal level of strain, increased colla- 1 1 2 1 Ryan Pewowaruk , Amy Hein , Claudiq Korcarz , Adam Gepner. gen content is required to maintain luminal diameter and avoid dilata- William S. Middleton Memorial Veterans Hospital, Madison, United tion (2 in Fig. B). We evaluated this hypothesis, expecting hypertensive States, University of Wisconsin School of Medicine and Public Health, rat aorta to exhibit less collagen strain under normotensive conditions Madison, United States compared to normotensive control (3 in Fig. B). Methods: One normotensive (NT, Wistar) and one hypertensive (HT, Background: Vascular smooth muscle tone may play an important ZSF1 lean [5]) 22-week-old rat abdominal aorta were stretched to role in the physiology of increased arterial stiffness that occurs with in vivo-like length and pressurised to 100 mmHg. Three-dimensional aging. This study evaluated the impact of smooth muscle tone on collagen structure was then imaged by second harmonic generation arterial stiffness in older individuals following nitroglycerin induced using a two-photon microscope. vasodilation in elastic and muscular arteries. Results: At 100 mmHg, the HT artery visibly displayed a thicker colla- Methods: 40 older Veterans (> 60 years old), without known cardio- gen layer and curlier collagen fibres than the NT artery (Fig. C-F), sug- vascular disease, were included in this study. 20 were hypertensive gesting lower collagen fibre strain at normotensive pressures (3 in Fig. (70.8 ± 6.6 years, 10 female) and 20 were normotensive controls B). (72.0 ± 9.3 years, 8 female). Nitroglycerin (NTG) induced changes in Conclusions: Strain-dependent collagen degradation may be a key arterial stiffness were measured locally with vascular ultrasound in process driving hypertension-induced arterial remodelling. the carotid and brachial arteries, and regionally by carotid-femoral pulse wave velocity (cfPWV ) by tonometry. Results: With NTG, both hypertensive and normotensive control Vet- erans showed increased carotid PWV (6.4 ± 1.3 m/s to 7.2 ± 1.4 m/s, Δ 0.8 ± 1.1 m/s, p = 0.007) and cfPWV (8.6 ± 1.9 m/s to 9.5 ± 2.4 m/s, Δ 0.9 ± 2.3 m/s, p = 0.020) but did not change brachial PWV (11.2 ± 2.4 m/s to 11.1 ± 2.2 m/s, Δ − 0.2 ± 2.5 m/s, p = 0.72). The carotid artery dilated more in control participants than hypertensive Veterans (Δ 0.54 ± 0.19 mm vs 0.42 ± 0.12 mm, p = 0.022). Brachial artery dilation was similar, (Δ 0.55 ± 0.26 mm vs 0.51 ± 0.20 mm, p = 0.46). Conclusion: In older Veterans, without known cardiovascular dis- ease, NTG induced vasodilation increased elastic artery stiffness and did not change muscular artery stiffness. Increased central arterial stiffness and reduction in the arterial stiffness gradient could offset some of the benefits of lowering blood pressure in older patients who are prescribed vasodilators as an antihypertensive therapy. Elastic artery stiffening with vasodilation warrants further investiga- tion as it may be important for antihypertensive medication selec- tion and influence CVD development. A: Straight-but-not-overstretched collagen experiences minimal degradation [3]. B: Diameter maintenance in hypertension requires additional collagen at minimum-degradation strain. More and curlier collagen in hypertension (E–F) than normotension (C-D). References 1. Intengan and Schiffrin. Vascular remodeling in hypertension. Hypertension. 2001;38:581–587. 2. Nissen et al. Increased turnover of arterial collagen in hypertensive rats. Proc Natl Acad Sci USA. 1978;75:451–453. 3. Gaul et al. Strain mediated enzymatic degradation of arterial tissue. Acta Biomater. 2018;77:301–310. 4. Gaul et al. Pressure‑induced collagen degradation in arterial tissue as a potential mechanism for degenerative arterial disease progression. J Mech Behav Biomed Mater. 2020;109:103,771. Graphic abstract overviewing 1. research question, 2. methods, 3. 5. Hamdani et al. Myocardial titin hypophosphorylation importantly contrib‑ results, and 4. clinical implications of findings utes to heart failure with preserved ejection fraction in a rat metabolic risk model. Circ Heart Fail. 2013;6:1239–1249. Reference Pewowaruk RJ, Gepner AD. Smooth muscle tone alters arterial stiffness: the Keywords: Remoddeling strain collagen degradation importance of the extracellular matrix to vascular smooth muscle stiff‑ ness ratio. J Hypertens. 2022 Mar 1;40(3):512–519. Keywords: Vascular stiffness, hypertension, vasodilation, smooth muscle A rtery Research P.025 arterial elastance, Ea, and end-systolic elastance, Ees were computed ® ® Performance of pOpmetre versus SphygmoCor to detect central during rest, exercise, and recovery. arterial stiffness using central aortic pressures Results: At rest, subjects with Ipc-PH or No PH tended to have lower 1 2 2 3 ZC and Ea than those with PAH (Fig. 1A&C); all Ees values were simi- Mathilde Laime , Hasan Obeid , Imad Abi‑Nasr , Hakim Khettab , Magid 2 3 4,5 lar (Fig. 1b). During exercise, Zc decreased in the subject with No PH, Hallab , Pierre Bout ouyrie , Loukman Omarjee whereas it increased in those with Ipc-PH and did not change in those University Bretagne Occidentale, Laboratoire ORPHY, Brest, France, with PAH. During exercise, both Ees and Ea increased for all subjects 2 3 Clinique Bizet, Cardiology unit, Paris, France, Pharmacology department, but the increase in Ea was larger than the increase in Ees for both the European Georges Pompidou Hospital and Assistance Publique Hôpitaux PAH and Ipc-PH groups, suggesting RV:PA uncoupling. Interestingly, de Paris, Paris Cardiovascular Research Center (PARCC), Paris, France, Univ the changes in ZC and Ees/Ea were inversely related in Ipc-PH during Rennes, CHU Rennes, INSERM CIC1414, Vascular Medicine Department, exercise. Rennes, France, Vascular Medicine Department, Redon Hospital, 35600, Conclusions: With the limitation that the sample size is small, our find- Redon, Redon, France ings suggest that analysis of pulsatile pulmonary hemodynamics and RV:PA coupling with exercise can reveal distinctive PH phenotypes and Central arterial stiffness is an independent predictor of cardiovascular have diagnostic value. and total mortality. It can be diagnose directly by aortic pulse wave velocity (aPWV ) or indirectly by central aortic pressures (CAP). SphygmoCor , a non-invasive device using applanation tonometry, is the gold standard to measure CAP. However, its complexity limits its use in clinical practice. The aim of this study is to evaluate the accuracy of a novel non- invasive device, pOpmètre (Axelife SAS, Saint-Nicolas de Redon, France), to measure CAP in suspected peripheral arterial disease (PAD) patients. Systolic, diastolic and central pulse pressures measured with pOpmè- ® ® tre are compared with those measured with SphygmoCor . In this pilot, monocentric, prospective study, 53 suspected PAD patients were included. Among them: i) 26 patients (age: 69 ± 10y; 65% men) were diagnosed with peripheral arterial obstructive disease (PAOD) defined by a toe-brachial index ≤ 0.7 and/or an ankle-brachial index (ABI) ≤ 0.9; ii) 10 patients (age: 74 ± 9y; 70% men) were diag- nosed with peripheral arterial stiffness (mediacalcosis) defined by an ABI > 1.4; iii) 20 patients (age: 55 ± 16; 40% men) without PAD diagno- sis. There was a significant correlation between systolic, diastolic and central pulse pressures measured by pOpmètre compared with those measured by SphygmoCor in PAD patients (respectively, R2 = [0.94, 1.00, 0.84]; p = [10e − 16, 10e − 16, 10e − 11]), peripheral arterial stiffness patients (respectively, R2 = [0.96, 1.00, 0.84]; p = [10e − 8, 10e − 13, 10e − 7]) and no PAD patients (R2 = [0.98, 1.00, 0.97]]; p = [10e − 12, 10e − 16, 10e − 8]). CAP assessed by pOpmètre could be used in clinical practice to References: detect central arterial stiffness in suspected PAD patients. [1] Rosenkranz, S et al., Circulation, 141(8):678–693, 2020. Reference [2] Al‑ Omary, MS et al., Hypertension, 75(6):1397–1408, 2020. McEniery CM, Cockcroft JR, Roman MJ, Franklin SS, Wilkinson IB. Central blood [3] Vanderpool, RR et al., Annals of Biomedical Engineering, 38(5):1854–1861, pressure: current evidence and clinical importance. Eur Heart J. 7 juill 2010. 2014;35(26):1719‑25. [4] Sabbahi, A et al., Expert Review of Respiratory Medicine, 14(3):317–327, Keywords: Central aortic pressure, Peripheral arterial disease Keywords: Impedance, Coupling, Hypertension, Exercise. P.027 Obesity, metabolic disorders and cardiovascular disease Analyses of pulsatile pulmonary hemodynamics and right ventricular function during exercise P.030 1 1 1 Christopher Lechuga , Farhan Raza , Mitchel J. Colebank , Naomi C. Relationship between aortic and carotid stiffness with measures Chesler. of adiposity in adolescents. The maciste study University of California, Irvine, Irvine, United States 1,2 3 3 Giacomo Pucci , Mariella Martina , Elisabetta Bianchini , Vincenzo 3 1,2 1,2 4 Gemignani , Marco D’Abbondanza , Rosa Curcio , Francesca Battista , Background: Pulmonary hypertension (PH) leads to a mismatched 5 1,2 Fabio Anastasio, Gaetano Vaudo right ventricular (RV)-pulmonary arterial (PA) relationship (uncou- pling), which increases mortality [1]. Current diagnostic strategies 1 Department of Medicine and Surgery—University of Perugia, Perugia, utilize pulmonary vascular resistance (PVR) [2] but disregard the oppo- 2 3 Italy, "Santa Maria" University Hospital, Terni, Italy, Institute of Clinical sition to pulsatile flow as well as response to exercise [3,4]. We hypoth- 4 Physiology—National Council of Research, Pisa, Italy, Sports Medicine— esize that pulsatile pulmonary hemodynamics during exercise and 5 University of Padua, Padua, Italy, Cardiology Division—Mondovì Hospital, their relationship to RV-PA coupling can differentiate PH phenotypes Cuneo, Italy and refine diagnoses. Methods: 13 adult subjects with precapillary PH (PAH; n = 5), isolated Background: We evaluated the differential association between arte - postcapillary PH (Ipc-PH; n = 5), or no PH (No PH; n = 1) performed rial stiffness, taken at different arterial segments (aortic and carotid), invasive cardiopulmonary exercise testing with echocardiography- with global and local measures of adiposity, accounting for BP as a based pulmonary vascular pressure-flow and catheter-based RV pres- mediator of the relationship between fat accumulation and increased sure–volume data collection. Characteristic impedance ZC, effective arterial stiffness. Artery Research Bessa LR, Cruz LAB, Lima RLS, Presta MCLF, Alves Filho AAO, Cunha, RCA, et al. Methods: 322 healthy Italian adolescents from the MACISTE Study Correlation between Neck Circumference and Pulse Wave Velocity: A (Metabolic and Cardiovascular Investigation at School, TErni), were Population‑based Study. Rev Artery Research 2020. evaluated. BMI, waist, hip and neck circumferences (NC) were taken Instituto Brasileiro de Geografia e Estatística (IBGE). CensoIBGE 2010. Brazil: as measures of adiposity. Laboratory measures of adiposity were also IBGE; 2010. collected. Arterial stiffness was measured through carotid-femoral pulse wave velocity (applanation tonometry, SphygmoCor), and at the Keywords: Obesity, Pulse wave speed, Arterial stiffness carotid level (Cardiovascular suite, Quipu, Italy). Results: Mean age 17 ± 1.4 years, 56% boys, 40 (12%) with overweight. All central and peripheral measures of BP were higher in overweight vs normoweight (all p < 0.01) excluding peripheral and central DBPs, P.032 which were lower in overweight. The aortic-to-brachial pulse pressure In vivo measurement of blood pressure and pulse wave velocity amplification was reduced in overweight vs normoweight (1.51 ± 0.13 in streptozotocin‑induced type 1 diabetes in mice vs 1.58 ± 0,13, p < 0.01). Carotid and aortic stiffness were positively cor - 1,2 1,3 3,4 related with anthropometric and laboratory measures of adiposity. Margarita G. Pencheva , Eline Berends , Peter Leenders , Myrthe M. 1,2 2 2,5 After adjustment for MAP, only NC remained associated with carotid van der Bruggen , Koen W.F. van der Laan , Alessandro Giudici , Koen 2 3 2,6 1 (β = 0.24, p < 0.01) and aortic stiffness (β = 0.16, p = 0.02). After adjust- D. Reesink , Sébastien Foulquier , Bart Spronck , Casper G. Schalkwijk ment for central PP, only carotid (β = 0.15, p = 0.04), but not aortic stiff- Depatrment of Internal Medicine, CARIM School for Cardiovascular ness (β = 0.12, p = 0.07) was associated with NC. Diseases, Maastricht University, Maastricht, The Netherlands, Dept. Conclusions: Arterial stiffness, when assessed at different levels of of Biomedical Engineering, CARIM School for Cardiovascular Diseases, central arteries, showed site-specific associations with measures of Maastricht University, Maastricht, The Netherlands, Dept. of Pharmacol‑ body fat adiposity. NC was the only measure of adiposity to show a ogy and Toxicology, CARIM School for Cardiovascular Diseases, Maastricht BP-independent association with carotid stiffness. Carotid stiffness is University, Maastricht, The Netherlands, Dept. of Biochemistry, CARIM a promising marker of pressure-independent vascular damage pro- School for Cardiovascular Diseases, Maastricht University, Maastricht, The moted by overweight status. Netherlands, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands, Macquarie Medical School, Keywords: Adolescents, adiposity, carotid stiffness, blood pressure Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia P.031 Background: In humans, type 1 diabetes (T1D) is associated with Obesity and Cardiovascular Risk Factors in the Outcome arterial stiffening as assessed by carotid-femoral pulse wave velocity of Arterial Stiffness (cfPWV) [1]. To experimentally study the underlying mechanism of this 1 1 1 Gabriela Portugal , Mariana Mendes , Laysa Rebouças , Lucelia stiffening, we investigated blood pressure (BP) and cfPWV in strepto - Magalhães zotocin (STZ)-induced diabetes in mice. Methods: Twenty-four 9-week-old male C57BL/6 J mice were divided Uniftc, Salvador, Brazil equally among diabetic (induced through once-daily 50 mg/kg STZ Obesity is one of the biggest health problems in the world. It is injections for five days) and control (sham injections using citrate constituted as the second most important risk factor for the devel- buffer) groups, and were kept to an age of 24 weeks. Fasting glucose opment of chronic non-communicable diseases. In this sense, it is was measured every 4–5 weeks via tail blood collection with levels assumed that the increase in arterial stiffness is on the path between of 15 mmol/L and higher considered diabetic. Non-invasive tono- obesity and cardiovascular diseases. The objective of this study was metric cfPWV was measured in anaesthetised animals (1% isoflurane) to evaluate the correlation between obesity and cardiovascular risk 24 h prior to euthanasia; tail-cuff BP was measured directly prior to factors with arterial stiffness in patients treated at a teaching clinic euthanasia. in the university center, Salvador-Ba, in 2022. This is an observa- Results: Diabetic mice exhibited higher fasting glucose than controls tional, cross-sectional and analytical study. The studied population (p < 0.0001, two-way ANOVA with Tukey post-hoc test; Fig. A). There comprised individuals residing in the Valley of Ogunjá neighbor- was no difference in systolic BP (110 ± 4 vs. 104 ± 3 mmHg, p = 0.26, hood, Acupe in Brotas, both sexes, over 18 years of age and obese. mean ± SE, unpaired t-test) and cfPWV (2.60 ± 0.14 vs. 2.55 ± 0.11 m/s, The indicators of obesity were: waist circumference (women > 88 cm p = 0.80) between diabetic and control mice (Fig. B-C). and men > 90 cm), cervical (> 34 cm in women and > 37 cm in men), Discussion: In the popular animal model of STZ-induced T1D, existing waist-hip ratio (> 0.80 in women and > 0.95 in men), body mass literature on systolic BP is not consistent [2,3]. Literature about cfPWV index (BMI) (> 30 kg/m ) and evaluation of the carotid-femoral pulse is limited: in contrast to our data, one report showed an STZ-induced wave velocity (PWV ) (> 10 m/s). The results obtained denote a direct increase in ultrasound-derived cfPWV [4]. Discrepancies between stud- to statistically significant linear correlation: waist circumference indi- ies could be due to different methods of measuring BP and cfPWV [5]; cator associated with PWV (p value 0.055), waist-hip ratio (p-value the choice of measurement methods therefore needs critical appraisal. 0.003), cervical circumference (p-value 0.004). Only the BMI indicator Conclusion: In the murine model of STZ-induced T1D, we did not find associated with PWV (p value 0.584) was not statistically significant. elevated BP or increased arterial stiffness. It is concluded that the indicators of abdominal and cervical circum- ference and waist-hip ratio obtained statistical significance when attributed to PWV and can be used as indicators of arterial stiffness. References Associação Brasileira para o Estudo da Obesidade e Síndrome Metabólica. Mapa da Obesidade [internet]. Higienópolis: 2021 [citied: Out 24 2021]. Available from: https:// abeso. org. br/ obesi dade‑e‑ sindr ome‑ metab olica/ mapa da‑ obesidade/. Brasil. Saúde prepara ações para controle do excesso de peso e da obesidade Despite clearly increased fasting blood glucose (A), streptozotocin- [Internet]. Brasília: Ministério da Saúde,2020 [cited: Out 24 2021]. Available induced diabetic mice did not show increased blood pressure (B) from: https:// aps. saude. gov. br/ notic ia/ 10137#: ~: text=O% 20Min ist% C3% or arterial stiffness (C). Shown are mean ± SE; ****p < 0.0001; ns, not A9rio% 20da% 20Sa% C3% BAde% 20ir% C3% A1,de% 20pro mo% C3% A7% significant. C3% A3o% 20de% 20da% 20sa% C3% BAde. A rtery Research References: LVET (left) and iLVET (right) against EF Simpson, effect direction 1. Tougaard NH, Theilade S, Winther SA, Tofte N, Ahluwalia TS, Hansen TW, et al. between second and first visit. Gray arrows show individual meas- J Am Heart Assoc. 2020;9:e017165. urements, the blue arrow shows the mean effect over 37 subjects. 2. Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW, Coffman TM. Am J Physiol Renal Physiol. 2010;298:F788‑795. References 3. Zhong F, Chen H, Wei C, Zhang W, Li Z, Jain MK, et al. Kidney Int. [1] A. Haiden, B. Eber, and T. Weber, ‘U‑Shaped Relationship of Left Ventricu‑ 2015;87:382–395. lar Ejection Time Index and All‑ Cause Mortality’, American Journal of 4. Heath JM, Sun Y, Yuan K, Bradley WE, Litovsky S, Dell’Italia LJ, et al. Circ Res. Hypertension, vol. 27, no. 5, pp. 702–709, Mai 2014, https:// doi. org/ 10. 2014;114:1094–1102. 1093/ ajh/ hpt185. 5. Leloup AJ, Fransen P, Van Hove CE, Demolder M, De Keulenaer GW, Schrijvers [2] A. Bauer, B. Hametner, T. Weber, and S. Wassertheurer, ‘Method Comparison DM. Hypertension. 2014;64:195–200. and Validation of the Determination of Ejection Duration from Oscillo‑ metric Measurements’, IFAC‑PapersOnLine, vol. 51, no. 2, pp. 343–348, Jan. Keywords: Diabetes, streptozotocin, blood pressure, pulse wave 2018, https:// doi. org/ 10. 1016/j. ifacol. 2018. 03. 059. velocity [3] Lewis R P, Rittogers S E, Froester W F, and Boudoulas H, ‘A critical review of the systolic time intervals.’, Circulation, vol. 56, no. 2, pp. 146–158, Aug. 1977, https:// doi. org/ 10. 1161/ 01. CIR. 56.2. 146. P.033 Pulse waveform analysis for monitoring of left ventricular function in patients with severely reduced ejection fraction P.034 Sex‑specific association between the metabolic score for insulin 1,4 1 1 Stefan Orter , Bernhard Hametner, Siegfried Wassertheurer , Kathrin resistance and arterial stiffness in middle‑aged adults 2 3 3 4 Danninger , Antonis Ar gyris , Athanase Protogerou , Eugenijus K aniusas , with metabolic syndrome 2 2 Ronald Binder, Thomas Weber 1 2,3 3 Jurgita Mikolaitytė , Agnė Laučytė‑Cibulskienė , Ligita Ryliškytė , Center for Health & Bioresources, AIT Austrian Institute of Technology, 1,3 Jolita Badarienė Vienna, Austria, Cardiology Department, Klinikum Wels‑Grieskirchen, 3 1 Wels, Austria, Cardiovascular Prevention and Research Unit, Laiko Hospi‑ State Research Institute Centre for Innovative Medicine, Vilnius, Lithu‑ 4 2 tal, Athens, Greece, Institute of Biomedical Electronics, Vienna University ania, Department of Nephrology, Lund University, Malmö, Sweden, of Technology, Vienna, Austria Faculty of Medicine, Vilnius University, Vilnius, Lithuania Background: Impaired systolic function of the left ventricle leads to Background: The Metabolic Score for Insulin Resistance (METS-IR) is shortening of the left ventricular ejection time (LVET ) and heart rate a non-insulin-based metabolic index used as a substitution marker of adjusted LVET (iLVET)[1]. The aim of this study is the investigation insulin resistance and cardiometabolic risk. Previous studies have sug- of the improvement in left ventricular function using radial pulse gested that insulin resistance is significantly related to the develop - waveforms compared to improvement assessed by ejection fraction ment and progression of coronary atherosclerosis and adverse plaque (EF). characteristics. The main objective of this study was to evaluate the Methods: 37 patients (7 females) with heart failure (HF) with reduced sex-specific relationship between METS-IR and arterial parameters in ejection fraction (HFrEF) were treated according to HF guidelines. EF the middle-aged Lithuanian population with metabolic syndrome. and its changes under treatment were monitored with echocardiogra- Methods: A total of 2064 subjects (1136 women and 928 men). phy (EPIQ, Philips, Simpson method with apical 4-chamber view), and Anthropometric, laboratory testing, and cardiovascular risk factors LVET was monitored with tonometry (SphygmoCor, AtCor Medical, along with arterial parameters (carotid-radial pulse wave velocity method based on numerical derivatives)[2]. Furthermore, LVET was (crPWV ), carotid-femoral pulse wave velocity (cfPWV ), carotid intima- adjusted for heart rate[3]. Visualization of differences between first media thickness (CIMT), ankle-brachial index (ABI), cardio-ankle vas- and second visit was done by 4-quadrant plots (Fig. 1) and concord- cular index (CAVI) and atherosclerotic plaques) were evaluated. ance rate was calculated. Results: After stratifying subjects into sex-specific METS-IR quartiles, Results: Patients mean age and body height were 54 years, and we observed statistically significant differences in all arterial param- 174 cm respectively. Their average weight decreased from 89 to 88 kg. eters among METS-IR quartiles, except for crPWV in men (p = 0.533). Measured basic parameters on first and second visit were HR (68BPM Differences between men and women in the METS-IR quartiles were vs. 60BPM), SBP (128 mmHg vs. 128 mmHg), DBP (81 mmHg vs. observed only in cfPWV (p < 0.05), CAVI (p < 0.05), and CIMT (p < 0.001). 76 mmHg), EF (25% vs. 42%), LVET (0.266 s vs. 0.289 s), iLVET (0.380 vs. In a fully adjusted linear regression analysis, METS-IR was associated 0.389), percentage of patients with betablocker intake (76% vs. 97%), with CAVI in both men (p = 0.005) and women (p < 0.001). However, and percentage of patients with ACE-I/ARB/ARNI intake (92% vs. 97%). ABI—only in men (p = 0.040), and CIMT – in women (p = 0.025). The mean timespan between first and second measurements was Conclusion: Insulin resistance measured by METS-IR is associated with 100 days. A concordance rate of 0.84 for LVET and 0.65 for iLVET was CAVI in both men and women in the middle-aged Lithuanian popula- observed. tion with metabolic syndrome. Additionally, in men, it is also associ- Conclusions: Automatically measured LVET and iLVET from radial ated with ABI, whereas in women – with CIMT. pressure waveforms is suitable for monitoring the improvement of EF with medical treatment in HFrEF. Keywords: Arterial stiffness, cardio-ankle vascular index, carotid intima-media thickness, ankle-brachial index, Metabolic Score for Insu- lin Resistance P.036 The effects of different types of calorie restriction on atherosclerosis‑related miRNAs in mice 1 2 2 Dilara Buse Durdabak , Nazim Arda Keles , Soner Dogan , Bilge Guvenc Tuna Department of Biophysics, School of Medicine, Yeditepe University, Istanbul, Turkey, Department of Medical Biology, School of Medicine, Yeditepe University, Istanbul, Turkey Artery Research Atherosclerosis is a chronic inflammatory blood vessel disease.Stud- Pulse-Wave-velocity (cfPWV), central pulse pressure (CPP) (Sphyg- ies highlight the importance of epigenetic modifications specifically mocor); 6. Autofluorescence- Advanced glycation end-products miRNAs in the development and progression of atherosclerosis.Calo- (AGE-Reader); 7. Carotid intima-media thickness (CIMT). We per- rie restriction(CR) is one of the best-known interventions to prolong formed one-way ANOVA to compare differences in the three groups. lifespan and impact lowering the risk of atherosclerosis.In the present Results: Demographics and anthropometry (BMI and waist circum- study, the effects of different types of CR on atherosclerosis-related ference) were comparable in all three groups. When compared to miRNA were studied. Groups 2 and 3, In Group 1: Troponin and the red cell distribution width (RDW) was higher (p < 0.05); Sphygmocor based cfPWV & Female mice were enrolled into three groups; ad-libitum (AL), Chronic- CPP, was higher (p < 0.001); RHI-EndoPAT based AI (@75) was higher CR (CCR, 15% CR), and Intermittent-CR (ICR) which 60% CR was applied and HRV(SDNN) was lower (p < 0.05); AGE was higher (p < 0.01) (see for one week (ICR-R, restricted) followed by three weeks of AL feed- Fig. 1). ing (ICR-RF, refeed).Blood and brain samples were collected at week Conclusion: Measures of arterial-stiffness (cf-PWV & AI@75) and HRV 49/50 to measure miRNA expression levels using Affymetrix GeneChip are more significantly impaired in DM when compared to hyper - miRNA 4.1 Array.The targets of differentially expressed(DE) miRNAs tension/hyperlipidemia, one year post COVID-19 recovery. These that are enriched in atherosclerosis-related molecular pathways were measures are higher when compared to similar matched diabe- analyzed. tes patients with no history of COVID-19 infection. COVID-19 DM In blood, a total of 12 miRNAs were DE among dietary groups.There patients need to be followed up to study long-term impact on vas- were common miRNAs that differ in dietary regimes when compared cular complications and autonomic neuropathy. to the AL group; miR-709(17,09-fold higher), miR-30b-5p(7,12-fold lower), and miR-19b-3p(5,72-fold lower) in CCR.The overexpression of miR-709 is shown to have a cardioprotective effect , while miR- 2 3 30b-5p and miR-19b-3p are considered pro-atherosclerotic.GO- KEGG analyses revealed that targets of atherosclerosis-related miRNAs that were affected with CR were also enriched in aging and cancer- related molecular pathways.In the brain, a total of 6 miRNAs were dif- ferentially expressed.Interestingly, there was no significant change in atherosclerosis-related miRNAs between blood and brain. In conclusion, even though CR has different effects on blood and brain tissues, some common miRNAs might have protective effects on ath- erosclerosis, suggesting the link between the brain and vascular axis. References 1. Li M, Chen H, Chen L, Chen Y, Liu X, Mo D. miR‑709 modulates LPS‑induced inflammatory response through targeting GSK ‑3β. Int Immunopharma‑ col. 2016 Jul;36:333–8. 2. Qi X, Wang H, Xia L, Lin R, Li T, Guan C, et al. miR‑30b ‑5p releases HMGB1 Table showing various vascular measures and figure showing box via UBE2D2/KAT2B/HMGB1 pathway to promote pro‑inflammatory plot on the pulse-wave-velocity in the three groups polarization and recruitment of macrophages. Atherosclerosis. 2021 May;324:38–45. 3. Wang J, Xu X, Li P, Zhang B, Zhang J. HDAC3 protects against atherosclerosis through inhibition of inflammation via the microRNA‑19b/PPARγ/NF‑κB axis. Atherosclerosis. 2021 Apr;323:1–12. Keywords: Atherosclerosis, calorie restrictions, miRNA P.037 Diabetes Mellitus is associated with relatively higher arterial stiffness when compared to hypertension or hyperlipidemia post‑recovery from COVID‑19 1,2 2,3 2,3 2 Rinkoo Dalan, Barnaby Young , David Lye , Bernhard Boehm. 1 2 Tan Tock Seng Hospital, Singapore, Singapore, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore, National Centre for infectious diseases, Singapore, Singapore Background: COVID-19, is associated with vascular dysfunction, arte- rial stiffness and worse outcomes in diabetes mellitus (DM) (1). We hypothesise that longer-term impact in COVID-19 DM patients will be worse when compared to other metabolic conditions, 1 year after recovery from COVID-19. Reference Methods: We recruited 63 patients belonging to the three groups: 1. Zota IM, Stătescu C, Sascău RA, et al. Acute and Long‑ Term Consequences group 1 – recovered COVID-19 DM-type 2, n = 14; Group 2- recov- of COVID‑19 on Arterial Stiffness‑A Narrative Review. Life (Basel). ered COVID-19, non-diabetes hypertension or hyperlipidemia, 2022;12(6):781. n = 29 and Group 3- non-COVID-19 DM, n = 14. Data collected: 1. Demographics, 2. Anthropometry, 3. Metabolic profile, 4. Reac - Keywords: COVID-19; arterial-stiffness, pulse-wave-velocity, tive Hyperaemia index (LnRHI), Augmentation index (AI@75), diabetes Heart Rate variability (HRV) (RHI-EndoPAT), 5. Carotid-femoral A rtery Research P.038 Clinical aspects Large artery stiffness using Sphgymocor technology shows higher augmentation index in pre‑diabetes and diabetes in multi‑ethnic P.042 Singapore Estimating pulse wave velocity in Community Pharmacies improves CV‑risk stratification compared to SCORE Ying Jie Chee , Rinkoo Dalan 1,2 3 3 3 Enrique Rodilla , Manuel Adell, Vicente Baixauli , Otón Bellver , Lidón Tan Tock Seng Hospital, Singapore, Singapore 3 3 3 3 Castillo , Santiago Centelles , Edelmira Córcoles , Rosario Hernández , 3 3 3 3 Background: The Sphygmocor technology uses applanation tonometry Sara Martínez , Zeneida Perseguer , Rosa Prats , Javier Reig , Desiré 3 3 2,3 2 2 to measure large artery stiffness. Although the carotid-femoral pulse Ruiz , Fanny Ruiz , Luis Salar , José‑Antonio Costa , José Chordá , Julio 1 1 3 wave velocity (cfPWV) is higher in diabetes, an association with pre-dia- Vicente , Ana Gómez , Maite Climent betes has not been observed.(1,2) There is limited data on augmentation 1 2 Hospital Universitario de Sagunto, Puerto De Sagunto, Spain, Universi‑ index (AIx). We aimed to study the correlation of arterial stiffness among dad Cardenal Herrera‑CEU, CEU Universities, Moncada ( Valencia), Spain, healthy, pre-diabetes, or diabetes in multi-ethnic Singapore. Sociedad Española de Farmacia Familiar y Comunitaria (SEFAC‑Valencia), Methods: Population: n = 130; Age = 44.8 (9.6) years; Male = 41 (31%), Valencia, Spain Chinese = 93, Indians = 12, Malays = 15, Others = 10. All participants underwent a standard 75 g oral glucose tolerance test and applanation Background: Arterial stiffness is considered to be an intermediate tonometry to assess cfPWV, central pulse pressure (CPP) and AIx. One- marker of CV risk with independent prognostic value. The objective of way ANOVA was done to study the differences in the arterial measure - this study is to assess whether the estimation of arterial stiffness can ments based on diabetes status. improve CV risk stratification compared to SCORE in patients at Commu- Results: Healthy (n = 81), Prediabetes (n = 27), Diabetes (n = 22). While nity Pharmacies. cfPWV was higher in diabetes (mean (SD): 7.2(1.6)) compared to absence Methods: Observational prospective epidemiological study in which of diabetes (6.5(1.0)); p < 0.01), there was no difference between healthy consecutive individuals entering a participating Community Pharmacy 6.5(1.1) and pre-diabetes (6.4(1.0)); p > 0.01. An increasing trend was are offered a voluntary measurement of blood pressure and estimation seen in AIx, healthy (mean (SD): 9.5(4.3)) < pre-diabetes (mean (SD): of pulse wave velocity by oscillometry (AGEDIO, IEM ) to stratify their 11.1(5.4)) < diabetes (mean (SD):13.1(7.0)); p < 0.01. No statistically signifi- CV risk according to SCORE compared to the use of arterial stiffness. cant difference was seen in CPP (p > 0.01). Results: After nine months of recruitment, data from 923 patients Discussion: AIx may reflect early markers of impaired glucose tolerance (173 women, 102 men) were collected. 16/122 (13.1%) patients under or pre-diabetes. Moreover, as AIx is determined by the properties of the 40 years and 72/364 (19.8%) over 65 years of age presented pathologi- distal vasculature, it may be used as an early marker of distal circulatory cal stiffness and could be classified as high-risk, even though being dysfunction involving the small arterioles, which precede abnormalities out of the age-range of SCORE. Of the 437 (47.3%) patients who were in pulse wave velocities. AIx can be a valuable marker of early vascular susceptible to calculating SCORE, 42/437 patients (9.6%) presented dysfunction, especially among individuals with pre-diabetes. Further pathological arterial stiffness. Cholesterol values were available in 281 studies are needed to understand the mechanistic basis of this trend. patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. Conclusions: More than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, there- fore, high CV risk, when SCORE only detected it in 2.1%. Therefore, esti- mating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE. Fig. 1 (A) augmentation index and (B) pulse wave velocity in healthy, pre‑ diabetes and diabetes References 1. Henry RM, Kostense PJ, Spijkerman AM, Dekker JM, Nijpels G, Heine RJ, et al. Arterial stiffness increases with deteriorating glucose tolerance status: the Hoorn Study. Circulation. 2003 Apr;107(16):2089–95. https:// doi. org/ 10. 1161/ 01. CIR. 00000 65222. 34933. FC. 2. Prenner SB, Chirinos JA. Arterial stiffness in diabetes mellitus. Atherosclerosis. 2015 Feb;238(2):370–9. https:// doi. org/ 10. 1016/j. ather oscle rosis. 2014. 12. Keywords: Arterial stiffness, augmentation index, pre-diabetes, diabetes Artery Research References Background: Remote ischemic preconditioning (RIPC) is a phenom- ‑ Rodilla Sala E, Adell Alegre M, Giner Galvañ V, Perseguer Torregrosa Z, Pascual enon in which short episodes of ischemia are applied to distant organs Izuel JM, Climent Catalá MT, et al. Arterial stiffness in normotensive and to prepare target organs for more prolonged ischemia and induce hypertensive subjects: frequency in community pharmacies. Med Clin protection against ischemia–reperfusion injury [1]. The aim of this (Barc) 2017;149:469–76 [Article in English, Spanish]. study was to evaluate whether preoperatively performed RIPC affects ‑ Nunan D, Fleming S, Hametner B, Wassertheurer S. Performance of pulse metabolome following vascular surgery and assess if metabolomic wave velocity measured using a brachial cuff in a community setting. changes correlate with heart and kidney injury markers. Blood Press Monit. 2014;19:315–9. Methods: A randomized-controlled, double-blinded trial was con- ducted in the Tartu University Hospital. Patients undergoing open Keywords: Pulse wave velocity, brachial oscillometry, risk stratifica- surgical repair of abdominal aortic aneurysm, surgical lower limb tion, pharmacies revascularization, and carotid endarterectomy were recruited. A RIPC consisting of four cycles of 5 min of ischemia followed by 5 min of rep- erfusion was applied before the operation. The blood was collected P.043 preoperatively and approximately 24 h postoperatively. The metabo- Evaluation of office and ambulatory central blood pressure lome was analyzed with the AbsoluteIDQ p180 Kit. by two methods and their changes after lifestyle or medical Results: The final analysis included 45 patients from the RIPC and 47 interventions in hypertension from the sham group. Baseline characteristics and values of metabo- 1 2 1 3 János Nemcsik , Helga Gyöngyösi , Dóra Batta , Andrea László , Dr. lites were statistically similar between groups. RIPC did not cause sta- 1 1 4 5 Péter Torzsa , Beáta Kőrösi , Zsófia Nemcsik‑Bencze , Orsolya Cseprekál , tistically significant changes in metabolites 24 h postoperatively. There András Tislér was a significant positive correlation between the change Kynure - nine/Tryptophan ratio and the changes of hs-Troponin T (r = 0.570, p Semmelweis University, Department Of Family Medicine, Budapest, Hun‑ ˂0.001), NT-proBNP (r = 0.552, p ˂0.001), Cystatin C (r = 0.534, p ˂0.001) gary, Semmelweis University, Faculty of Medicine, Budapest, Hungary, 3 4 and Beta-2-Microglobulin (r = 0.504, p ˂0.001). Norisana‑ MVZ Rosenau, Nuremberg, Germany, Semmelweis University, Conclusions: Preoperatively performed RIPC did not significantly Department of Neuroradiology, Budapest, Hungary, Semmelweis Univer‑ affect metabolome 24 h after vascular surgery. The positive linear sity, Department of Transplantation and Surgery, Budapest, Hungary, correlation between Kynurenine/Tryptophan ratio and heart and Semmelweis University, Department of Internal Medicine and Oncology, kidney injury markers suggests that the Kynurenine-Tryptophan Budapest, Hungary pathway can play a role in RIPC-associated cardio- and nephropro- Background: Central systolic blood pressure (cSBP) can be evaluated tective effects. in office and also in ambulatory condition, during 24-h monitoring. The aim of our study was to measure office brachial systolic BP (bSBP) Reference and cSBP in the office and brachial SBP and cSBP in 24-h setting