State Key Laboratory for Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Sci China Life Sci. 2018 Sep;61(9):1024-1029. doi: 10.1007/s11427-017-9285-1. Epub 2018 Apr 16.
Endothelial dysfunction is caused by many factors, such as dyslipidemia, endoplasmic reticulum (ER) stress, and inflammation. It has been demonstrated that endothelial dysfunction is the initial process of atherosclerosis. AMP-activated protein kinase (AMPK) is an important metabolic switch that plays a crucial role in lipid metabolism and inflammation. However, recent evidence indicates that AMPK could be a target for atherosclerosis by improving endothelial function. For instance, activation of AMPK inhibits the production of reactive oxygen species induced by mitochondrial dysfunction, ER stress, and NADPH oxidase. Moreover, activation of AMPK inhibits the production of pro-inflammatory factors induced by dyslipidemia and hyperglycemia and restrains production of perivascular adipose tissue-released adipokines. AMPK activation prevents endothelial dysfunction by increasing the bioavailability of nitric oxide. Therefore, we focused on the primary risk factors involved in endothelial dysfunction, and summarize the features of AMPK in the protection of endothelial function, by providing signaling pathways thought to be important in the pathological progress of risk factors.
内皮功能障碍是由多种因素引起的，如血脂异常、内质网（ER）应激和炎症。已经证明内皮功能障碍是动脉粥样硬化的初始过程。AMP 激活的蛋白激酶（AMPK）是一种重要的代谢开关，在脂质代谢和炎症中起着至关重要的作用。然而，最近的证据表明，AMPK 可以通过改善内皮功能成为动脉粥样硬化的靶点。例如，激活 AMPK 可抑制由线粒体功能障碍、内质网应激和 NADPH 氧化酶引起的活性氧的产生。此外，激活 AMPK 可抑制由血脂异常和高血糖引起的促炎因子的产生，并抑制血管周围脂肪组织释放的脂肪因子的产生。AMPK 的激活通过增加一氧化氮的生物利用度来防止内皮功能障碍。因此，我们专注于内皮功能障碍的主要危险因素，并通过提供被认为在危险因素的病理进展中很重要的信号通路，总结 AMPK 在保护内皮功能方面的特征。
