烟碱致动脉粥样硬化的N胆碱受体信号通路

Signaling pathway of acetylcholine receptors in atherosclerosis induced by nicotinic

动脉粥样硬化是一种血管炎症性疾病。烟碱(尼古丁)是香烟的主要成分之一,是许多心血管疾病(如动脉粥样硬化)的致病危险因素。最近的研究表明,烟碱可与细胞表面的烟碱型乙酰胆碱受体(nAChR)高度结合并加速动脉粥样硬化的发展,nAChR在血管的各类细胞中都有不同量的表达。因此,本综述总结nAChR及配体在烟碱致动脉粥样硬化的发病机制中的作用,以及基于nAChR的信号通路在相关细胞(如血管平滑肌细胞、内皮细胞、血小板及免疫细胞)中对动脉粥样硬化的作用,同时讨论这些通路是如何影响斑块的稳定和发展的。最后将讨论nAChR作为治疗动脉粥样硬化分子靶点的可能性。

Objective Atherosclerosis is an inflammatory disease in the vessel wall.Nicotine,a major component of cigarette smoke,is an independent risk factor for cardiovascular diseases including atherosclerosis.Recent studies have shown that nicotine （the addictive component of cigarettes） binds to high affinity cell-surface receptors and accelerates the atherogenic process.These receptors were called nicotinic acetylcholine receptors （nAChR） and expressed ubiquitously in almost all cells existing in the blood vessels.Therefore,the pro-atherogenic effects of nAChR pathway ligands were summarized which would enhance the understanding of the role of nicotine and nAChR in the pathophysiology of atherosclerosis.The signaling pathways underlying nAChR subunits in cells were described that play an important role in atherosclerosis,i.e.VSMCs,endothelial cells,platelets and immune cells.How these pathways converge on the growth and survival of atheromatous plaques were also discussed.Finally,the feasibility of nAChR ligands as therapeutic targets for atherosclerosis was summarized.