内皮素受体表达上调在冠状动脉痉挛中的作用机制

冠状动脉痉挛需要两个局部基本条件:(1)冠状动脉平滑肌高反应性,即冠状动脉对收缩物质刺激的敏感性增高,表现为收缩增强、甚至痉挛;(2)冠状动脉局部有足够可以引起平滑肌痉挛的收缩物质。内皮素1是人体内收缩血管最强的物质。研究证明,冠状动脉痉挛的危险因素(吸烟和高血脂)能激活ERK1/2信号通路,引起冠状动脉平滑肌细胞内皮素受体表达上调,从而导致血管对内皮素1刺激的敏感性和反应性明显增高,表现为收缩增强、甚至痉挛。本文综述了近年来有关内皮素受体表达上调与冠状动脉痉挛分子发病机制研究方面的新进展,为临床防治冠状动脉痉挛提供新思路和药物治疗新靶点。

The Role of Endothelin Receptor Upregulation in Coronary Artery Spasm

There are two local conditions for coronary artery spasmie. Firstly, coronary artery smooth muscle hyperresponsiveness that leads to coronary artery hypersensitive to vasoconstrictor substances results in increased contraction and even spasm and secondly, enough vasoconstrictor substances exists locally to induce coronary artery spasm. Endothelin-1 is the strongest vasoconstrictor substance in man. Studies have demonstrated that activation of extracellular signal-regulated kinases 1 and 2(ERK1/2)by risk factors for coronary spasm like hyperlipidemia and cigarette smoke can mediate endothelin receptor upregulation in coronary artery smooth muscle cells, subsequently results in significantly increased coronary artery sensitivity to endothelin-1 and leads to increase in vasoconstriction, and even vasospasm. Here, we review recent studies on the role of endothelin receptor upregulation in coronary artery spasm, which might provide new therapeutic targets and novel strategy for treatment of coronary artery spasm.