Heilongjiang Academy of Chinese Medicine, Harbin, 150000, China.
Brandeis University, Waltham, MA, 02453, USA.
Cell Stress Chaperones. 2023 Nov;28(6):675-688. doi: 10.1007/s12192-023-01384-3. Epub 2023 Sep 27.
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.
心肌微血管由单层内皮细胞组成,内皮细胞在维持血管屏障功能、管腔通畅、血管张力和心肌灌注方面发挥着关键作用。内皮功能障碍是心脏微血管损伤和糖尿病心肌病发展的关键因素。除了在葡萄糖氧化和能量代谢中的作用外,线粒体还参与细胞凋亡、细胞内离子处理和氧化还原平衡等非代谢过程。线粒体动力学和自噬负责调节线粒体的质量和数量,以响应高血糖。然而,在糖尿病内皮损伤和心肌微血管损伤过程中,这些内源性的体内平衡机制既能保护又能破坏非代谢线粒体的功能。本综述概述了线粒体动力学和自噬的分子特征和调控机制。此外,我们总结了各种研究的结果,表明异常的线粒体动力学和有缺陷的自噬导致了糖尿病内皮功能障碍和心肌微血管损伤的发生。最后,我们讨论了不同的治疗策略,旨在通过增强线粒体动力学和自噬来改善内皮稳态和心肌微血管功能。