Abstract
Myocardial microvessels are composed of a monolayer of endothelial cells, which play a crucial role in maintaining vascular barrier function, luminal latency, vascular tone, and myocardial perfusion. Endothelial dysfunction is a key factor in the development of cardiac microvascular injury and diabetic cardiomyopathy. In addition to their role in glucose oxidation and energy metabolism, mitochondria also participate in non-metabolic processes such as apoptosis, intracellular ion handling, and redox balancing. Mitochondrial dynamics and mitophagy are responsible for regulating the quality and quantity of mitochondria in response to hyperglycemia. However, these endogenous homeostatic mechanisms can both preserve and/or disrupt non-metabolic mitochondrial functions during diabetic endothelial damage and cardiac microvascular injury. This review provides an overview of the molecular features and regulatory mechanisms of mitochondrial dynamics and mitophagy. Furthermore, we summarize findings from various investigations that suggest abnormal mitochondrial dynamics and defective mitophagy contribute to the development of diabetic endothelial dysfunction and myocardial microvascular injury. Finally, we discuss different therapeutic strategies aimed at improving endothelial homeostasis and cardiac microvascular function through the enhancement of mitochondrial dynamics and mitophagy.
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This study was supported by the Chinese Academy of Chinese Medical Sciences Doctoral Talents Training Fund (grant number: 2021) and Special Program for Training Outstanding Young Talents of Chinese Academy of Traditional Chinese Medicine (ZZ16-YQ-021). Innovative cultivation project of Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences (2022s481). The funders had no role in paper design, data collection, data analysis, interpretation, and writing of the paper.
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Tong Wang, **nwei Wang, Tong Fu, Yanchun Ma, Qi Wang, and Shuxiang Zhang collected the data and related references. **ao Zhang, Hao Zhou, **ng Chang, and Ying Tong contributed to study concept and design, supervision of the study, literature search, and writing of the manuscript, obtained funding, and revised the final version of manuscript. All the authors read the article and approved the submission.
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Wang, T., Wang, X., Fu, T. et al. Roles of mitochondrial dynamics and mitophagy in diabetic myocardial microvascular injury. Cell Stress and Chaperones 28, 675–688 (2023). https://doi.org/10.1007/s12192-023-01384-3
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DOI: https://doi.org/10.1007/s12192-023-01384-3