The Second Affiliated Hospital of Heilongjiang, University of Chinese Medicine, Harbin, 150001, China.
Department of Vascular Medicine, Peking University Shougang Hospital, Beijing, 100144, China.
Angiogenesis. 2022 Aug;25(3):307-329. doi: 10.1007/s10456-022-09835-8. Epub 2022 Mar 18.
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.
冠状动脉微血管内皮功能障碍既是糖尿病的罪魁祸首，也是受害者，它可以通过促进血管收缩、促炎和促血栓形成反应，加速糖尿病相关的微血管和大血管并发症。线粒体功能障碍会引起氧化应激，破坏内皮细胞的代谢并激活细胞凋亡，从而加剧糖尿病患者冠状动脉微血管并发症的进展。线粒体质量监控（MQS）系统通过改变线粒体代谢、动力学（分裂和融合）、线粒体自噬和生物发生来应对应激。功能失调的线粒体容易发生分裂，从而产生两种不同类型的线粒体：一种具有正常的膜电位，另一种具有去极化的线粒体膜电位。线粒体融合和线粒体自噬可以恢复有缺陷的线粒体片段的膜电位和内稳态。线粒体生物发生可以逆转由线粒体自噬引起的线粒体数量减少。MQS 异常会诱导病理性的线粒体分裂、延迟的线粒体自噬、代谢受损和生物发生缺陷，从而促进不健康线粒体的积累和线粒体依赖性细胞凋亡的激活。在这篇综述中，我们研究了 MQS 对线粒体健康的影响，并探讨了 MQS 障碍与糖尿病患者冠状动脉微血管内皮功能障碍的关联。我们还讨论了使用新型 MQS 改变药物治疗糖尿病相关冠状动脉微血管内皮功能障碍的潜力。
