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18-03-2022 | Hyperglycemia | Review Paper

Molecular mechanisms of coronary microvascular endothelial dysfunction in diabetes mellitus: focus on mitochondrial quality surveillance

Authors: Danan Sun, Jin Wang, Sam Toan, David Muid, Ruibing Li, Xing Chang, Hao Zhou

Published in: Angiogenesis | Issue 3/2022

Abstract

Coronary microvascular endothelial dysfunction is both a culprit and a victim of diabetes, and can accelerate diabetes-related microvascular and macrovascular complications by promoting vasoconstrictive, pro-inflammatory and pro-thrombotic responses. Perturbed mitochondrial function induces oxidative stress, disrupts metabolism and activates apoptosis in endothelial cells, thus exacerbating the progression of coronary microvascular complications in diabetes. The mitochondrial quality surveillance (MQS) system responds to stress by altering mitochondrial metabolism, dynamics (fission and fusion), mitophagy and biogenesis. Dysfunctional mitochondria are prone to fission, which generates two distinct types of mitochondria: one with a normal and the other with a depolarized mitochondrial membrane potential. Mitochondrial fusion and mitophagy can restore the membrane potential and homeostasis of defective mitochondrial fragments. Mitophagy-induced decreases in the mitochondrial population can be reversed by mitochondrial biogenesis. MQS abnormalities induce pathological mitochondrial fission, delayed mitophagy, impaired metabolism and defective biogenesis, thus promoting the accumulation of unhealthy mitochondria and the activation of mitochondria-dependent apoptosis. In this review, we examine the effects of MQS on mitochondrial fitness and explore the association of MQS disorders with coronary microvascular endothelial dysfunction in diabetes. We also discuss the potential to treat diabetes-related coronary microvascular endothelial dysfunction using novel MQS-altering drugs.

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Title: Molecular mechanisms of coronary microvascular endothelial dysfunction in diabetes mellitus: focus on mitochondrial quality surveillance
Authors: Danan Sun
Jin Wang
Sam Toan
David Muid
Ruibing Li
Xing Chang
Hao Zhou
Publication date: 18-03-2022
Publisher: Springer Netherlands
Keyword: Hyperglycemia
Published in: Angiogenesis / Issue 3/2022
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-022-09835-8

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