Department of Pharmacology, Physiology & Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
Atherosclerosis. 2012 Dec;225(2):264-73. doi: 10.1016/j.atherosclerosis.2012.07.041. Epub 2012 Aug 14.
Smoking is a major risk factor for the development of atherosclerosis, stroke and myocardial infarction. Cigarette smoke consists of a complex mixture of about 4000 compounds. Out of these, polycyclic hydrocarbons, tobacco-specific nitrosamines, oxidizing agents and carbon monoxide have been implicated in the development of 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 are called nicotinic acetylcholine receptors (nAChRs) and are expressed ubiquitously in almost all cells existing in the blood vessels. The present review summarizes the pro-atherogenic effects of nAChR ligands such as nicotine and tobacco nitrosamines. The contribution of different nAChR subunits in plaque growth, progression and neovascularization are discussed in detail. The signaling pathways underlying the actions of the nAChRs ligands in blood vessels are also described. Finally, the feasibility of nAChR ligands as therapeutic targets for atherosclerosis is summarized. We believe that the information presented in this review is relevant for atherosclerosis patients who are active smokers, exposed to environmental tobacco smoke or use nicotine patches or gums for smoking cessation.
吸烟是动脉粥样硬化、中风和心肌梗死发展的主要危险因素。香烟烟雾由大约 4000 种化合物组成的复杂混合物组成。在这些化合物中，多环芳烃、烟草特异性亚硝胺、氧化剂和一氧化碳已被牵连到动脉粥样硬化的发展中。最近的研究表明，尼古丁（香烟中的成瘾成分）与高亲和力细胞表面受体结合，并加速动脉粥样硬化过程。这些受体被称为烟碱型乙酰胆碱受体（nAChRs），几乎在所有存在于血管中的细胞中都广泛表达。本综述总结了 nAChR 配体（如尼古丁和烟草亚硝胺）的促动脉粥样硬化作用。详细讨论了不同 nAChR 亚基在斑块生长、进展和新生血管形成中的作用。还描述了 nAChR 配体在血管中作用的信号通路。最后，总结了 nAChR 配体作为动脉粥样硬化治疗靶点的可行性。我们相信，对于活跃吸烟者、暴露于环境烟草烟雾或使用尼古丁贴片或口香糖戒烟的动脉粥样硬化患者，本综述中提供的信息是相关的。
