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

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

Research output: Contribution to journalReview articlepeer-review

60 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)307-329
Number of pages23
JournalAngiogenesis
Volume25
Issue number3
DOIs
StatePublished - Aug 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature B.V.

Keywords

  • Biogenesis
  • Coronary microvascular endothelial dysfunction
  • Diabetes
  • Mitochondrial dynamics
  • Mitochondrial metabolism
  • Mitochondrial quality surveillance
  • Mitophagy

PubMed: MeSH publication types

  • Journal Article
  • Review

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