Department of Cardiology, The First Hospital of Jilin University, No. 71 of Xinmin Street, Changchun, 13000, China.
Department of Experimental Pharmacology and Toxicology, College of Pharmacy, Jilin University, Changchun, 130000, China.
J Thromb Thrombolysis. 2023 Oct;56(3):388-397. doi: 10.1007/s11239-023-02862-2. Epub 2023 Jul 19.
Coronary microvascular endothelial cells (CMECs) react to changes in coronary blood flow and myocardial metabolites and regulate coronary blood flow by balancing vasoconstrictors-such as endothelin-1-and the vessel dilators prostaglandin, nitric oxide, and endothelium-dependent hyperpolarizing factor. Coronary microvascular endothelial cell dysfunction is caused by several cardiovascular risk factors and chronic rheumatic diseases that impact CMEC blood flow regulation, resulting in coronary microcirculation dysfunction (CMD). The mechanisms of CMEC dysfunction are not fully understood. However, the following could be important mechanisms: the overexpression and activation of nicotinamide adenine dinucleotide phosphate oxidase (Nox), and mineralocorticoid receptors; the involvement of reactive oxygen species (ROS) caused by a decreased expression of sirtuins (SIRT3/SIRT1); forkhead box O3; and a decreased SK/IK expression in the endothelium-dependent hyperpolarizing factor electrical signal pathway. In addition, p66Shc is an adapter protein that promotes oxidative stress; although there are no studies on its involvement with cardiac microvessels, it is possible it plays an important role in CMD.
冠状动脉微血管内皮细胞 (CMECs) 对冠状动脉血流和心肌代谢产物的变化作出反应，并通过平衡血管收缩剂（如内皮素-1）和血管扩张剂（前列腺素、一氧化氮和内皮依赖性超极化因子）来调节冠状动脉血流。冠状动脉微血管内皮细胞功能障碍是由多种心血管危险因素和慢性风湿性疾病引起的，这些因素影响 CMEC 的血流调节，导致冠状动脉微循环功能障碍 (CMD)。CMEC 功能障碍的机制尚不完全清楚。然而，以下可能是重要的机制：烟酰胺腺嘌呤二核苷酸磷酸氧化酶 (Nox) 和盐皮质激素受体的过度表达和激活；沉默信息调节因子 (SIRT3/SIRT1) 表达减少导致的活性氧 (ROS) 参与；叉头框 O3；以及内皮依赖性超极化因子电信号通路中 SK/IK 表达减少。此外，p66Shc 是一种促进氧化应激的衔接蛋白；尽管尚无关于其与心脏微血管关系的研究，但它在 CMD 中可能发挥重要作用。
