琥珀酸/GPR91轴在动脉粥样硬化中的研究进展

Research advances of the succinate/GPR91 axis in atherosclerosis

摘要:

动脉粥样硬化(As)为慢性、炎症性病理过程,是多种心血管疾病的共同病理学基础,严重危害人类健康。近年研究表明,三羧酸循环中间体参与As的发生发展进程。琥珀酸是连接三羧酸循环和线粒体呼吸链之间的关键中间体,缺血、缺氧、中毒和高血糖等病理情况下,琥珀酸在线粒体、胞质和细胞外积蓄,激活其特异性受体GPR91,影响细胞代谢及细胞命运。近年研究发现,高脂血症和As小鼠的血清琥珀酸含量均显著升高。本文主要综述琥珀酸/GPR91轴在与As进程密切相关的血小板活化、免疫与炎症以及高血压中的作用,以期为As的有效防治提供新的参考。

Abstract:

Atherosclerosis (As) was a chronic and inflammatory pathological process, which was the common pathological basis of various cardiovascular diseases, resulting in seriously endangers for human health. Recent studies have shown that tricarboxylic acid cycle intermediates play important roles in the initiation and progression of atherosclerotic lesions. Succinate was a key intermediate that connects the tricarboxylic acid cycle and the mitochondrial respiratory chain.Under pathological conditions such as ischemia, hypoxia, poisoning and hyperglycemia, succinate was accumulated in mitochondria, cytoplasm and extracellular, activating its specificity receptor GPR91 and affecting cell metabolism and cell fate. Recent studies have found that serum succinate levels in hyperlipidemia and As mice were significantly increased, which contribute to the pathological processes of As. This article mainly reviews the role of succinate/GPR91 axis in platelet activation, immunity and inflammation, and hypertension that are closely related to the process of As,which might benefit to provide new alternations for the prevention and treatment of As.