Involvement of mitochondrial dynamics and mitophagy in diabetic endothelial dysfunction and cardiac microvascular...

Endothelial cells (ECs), found in the innermost layer of blood vessels, are crucial for maintaining the structure and function of coronary microcirculation. Dysregulated coronary microcirculation poses a fundamental challenge in diabetes-related myocardial microvascular injury, impacting myocardial blood perfusion, thrombogenesis, and inflammation. Extensive research aims to understand the mechanistic connection and functional relationship between cardiac EC dysfunction and the development, diagnosis, and treatment of diabetes-related myocardial microvascular injury. Despite the low mitochondrial content in ECs, mitochondria act as sensors of environmental and cellular stress, influencing EC viability, structure, and function. Mitochondrial dynamics and mitophagy play a vital role in orchestrating mitochondrial responses to various stressors by regulating morphology, localization, and degradation. Impaired mitochondrial dynamics or reduced mitophagy is associated with EC dysfunction, serving as a potential molecular basis and promising therapeutic target for diabetes-related myocardial microvascular injury. This review introduces newly recognized mechanisms of damaged coronary microvasculature in diabetes-related microvascular injury and provides updated insights into the molecular aspects of mitochondrial dynamics and mitophagy. Additionally, novel targeted therapeutic approaches against diabetes-related microvascular injury or endothelial dysfunction, focusing on mitochondrial fission and mitophagy in endothelial cells, are summarized.