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Health and Cognition in Old AgeVascular Aging: Revealing the Role and Clinical Perspectives of the Urokinase System

Health and Cognition in Old Age: Vascular Aging: Revealing the Role and Clinical Perspectives of... [Cardiovascular diseases (CVD) are the most common cause of death among the elderly population in Western countries. Despite progress in managing some of the established risk factors like hypertension and hypercholesterolemia, the incidence of CVD is predicted to increase as the population ages. The aging process itself is associated with morphological and functional changes in the vasculature. Moreover, age-related changes render the cardiovascular system susceptible to damaging actions of risk factors and diseases. Vascular smooth muscle cells (VSMCs) are intrinsically involved in age-associated changes of the vasculature. With age, the VSMC phenotype shifts towards a pathophysiological synthetic phenotype characterized by migration, proliferation, release of inflammatory cytokines, and augmented extracellular matrix deposition. The molecular mechanisms underlying age-associated VSMC phenotypic changes remain unclear. Recent large-scale population studies showed a close correlation between the urokinase/urokinase receptor system and CVD, inflammation, aging, and mortality. In our research, we have identified a new link between the urokinase system and arterial wall changes during vascular remodeling and initiation/progression of atherosclerosis. The urokinase system exerts its function at different levels. Systemically, it modulates oxidative stress via regulation of paraoxonase 1 production by the liver. Locally in the blood vessel wall, the urokinase system modulates VSMCs towards the synthetic phenotype via proteasomal degradation of the transcription coactivator, myocardin. Furthermore, the urokinase system interferes with VSMC senescence that influences the outcome of vascular remodeling and the fate of atherosclerotic plaques. The variety of functions exerted by the urokinase system in the vascular wall makes it an attractive therapeutic target.] http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png

Health and Cognition in Old AgeVascular Aging: Revealing the Role and Clinical Perspectives of the Urokinase System

Part of the International Perspectives on Aging Book Series (volume 10)
Editors: Leist, Anja K.; Kulmala, Jenni; Nyqvist, Fredrica

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References (47)

Publisher
Springer International Publishing
Copyright
© Springer International Publishing Switzerland 2014
ISBN
978-3-319-06649-3
Pages
11 –24
DOI
10.1007/978-3-319-06650-9_2
Publisher site
See Chapter on Publisher Site

Abstract

[Cardiovascular diseases (CVD) are the most common cause of death among the elderly population in Western countries. Despite progress in managing some of the established risk factors like hypertension and hypercholesterolemia, the incidence of CVD is predicted to increase as the population ages. The aging process itself is associated with morphological and functional changes in the vasculature. Moreover, age-related changes render the cardiovascular system susceptible to damaging actions of risk factors and diseases. Vascular smooth muscle cells (VSMCs) are intrinsically involved in age-associated changes of the vasculature. With age, the VSMC phenotype shifts towards a pathophysiological synthetic phenotype characterized by migration, proliferation, release of inflammatory cytokines, and augmented extracellular matrix deposition. The molecular mechanisms underlying age-associated VSMC phenotypic changes remain unclear. Recent large-scale population studies showed a close correlation between the urokinase/urokinase receptor system and CVD, inflammation, aging, and mortality. In our research, we have identified a new link between the urokinase system and arterial wall changes during vascular remodeling and initiation/progression of atherosclerosis. The urokinase system exerts its function at different levels. Systemically, it modulates oxidative stress via regulation of paraoxonase 1 production by the liver. Locally in the blood vessel wall, the urokinase system modulates VSMCs towards the synthetic phenotype via proteasomal degradation of the transcription coactivator, myocardin. Furthermore, the urokinase system interferes with VSMC senescence that influences the outcome of vascular remodeling and the fate of atherosclerotic plaques. The variety of functions exerted by the urokinase system in the vascular wall makes it an attractive therapeutic target.]

Published: Jun 10, 2014

Keywords: Vascular Remodel; Proteasomal Degradation; Serum Response Factor; Contractile Phenotype; VSMC Proliferation

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