Nicotinic acetylcholine receptor signaling in atherogenesis

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.