Elucidating molecular mechanisms that alleviate cardiac microvascular dysfunction in diabetes: The potential benefit of targeting mitophagy and mitochondrial integrity

William B. Horton

doi:10.1111/apha.13983

Horton, William B.

2023-07-01 00:00:00

In this issue of Acta Physiologica, Li et al. report that L‐carnitine (LC) therapy reversed mitochondrial dysfunction and repaired cardiac microvascular injury in diabetic cardiomyopathy.1 Specifically, they describe how LC augmented PINK1‐Parkin‐dependent mitophagy by maintaining the PHB2‐PARL interaction via CPT1 in db/db mice.1 This is an interesting discovery that holds translational value given the growing recognition of mitophagy as a contributing factor to coronary microvascular dysfunction (CMD).2 Mitophagy is an autophagic response that specifically targets damaged and, therefore, potentially cytotoxic mitochondria.3 Interestingly, a recent in vitro study of human umbilical vein endothelial cells reported that mitophagy alleviated ischemia/reperfusion‐induced microvascular damage by improving mitochondrial quality control,4 suggesting that mitophagy may represent a key quality control pathway in the microcirculation.Along these lines, emerging clinical evidence now highlights two potentially interrelated findings: (1) mitochondrial dysfunction is common in people with diabetes5 and may be the primary cause of CMD4 and (2) mitochondrial dysfunction and CMD are each linked to heart failure with preserved ejection fraction, which is the most common heart failure phenotype in people with diabetes.6 While these observations are intriguing, the field is currently limited by a lack of clear mechanistic insight that may inform targeted therapies aimed at alleviating

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Acta Physiologica Wiley

http://www.deepdyve.com/lp/wiley/elucidating-molecular-mechanisms-that-alleviate-cardiac-microvascular-X8o1CgHQNj

$In this issue of Acta Physiologica, Li et al. report that L‐carnitine (LC) therapy reversed mitochondrial dysfunction and repaired cardiac microvascular injury in diabetic cardiomyopathy.1 Specifically, they describe how LC augmented PINK1‐Parkin‐dependent mitophagy by maintaining the PHB2‐PARL interaction via CPT1 in db/db mice.1 This is an interesting discovery that holds translational value given the growing recognition of mitophagy as a contributing factor to coronary microvascular dysfunction (CMD).2 Mitophagy is an autophagic response that specifically targets damaged and, therefore, potentially cytotoxic mitochondria.3 Interestingly, a recent in vitro study of human umbilical vein endothelial cells reported that mitophagy alleviated ischemia/reperfusion‐induced microvascular damage by improving mitochondrial quality control,4 suggesting that mitophagy may represent a key quality control pathway in the microcirculation.Along these lines, emerging clinical evidence now highlights two potentially interrelated findings: (1) mitochondrial dysfunction is common in people with diabetes5 and may be the primary cause of CMD4 and (2) mitochondrial dysfunction and CMD are each linked to heart failure with preserved ejection fraction, which is the most common heart failure phenotype in people with diabetes.6 While these observations are intriguing, the field is currently limited by a lack of clear mechanistic insight that may inform targeted therapies aimed at alleviating$

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Elucidating molecular mechanisms that alleviate cardiac microvascular dysfunction in diabetes: The potential benefit of targeting mitophagy and mitochondrial integrity

Elucidating molecular mechanisms that alleviate cardiac microvascular dysfunction in diabetes: The potential benefit of targeting mitophagy and mitochondrial integrity

Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

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Elucidating molecular mechanisms that alleviate cardiac microvascular dysfunction in diabetes: The potential benefit of targeting mitophagy and mitochondrial integrity

Elucidating molecular mechanisms that alleviate cardiac microvascular dysfunction in diabetes: The potential benefit of targeting mitophagy and mitochondrial integrity

References (11)

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