Angiogenic activity of nicotinic acetylcholine receptors: Implications in tobacco-related vascular diseases

Cigarette smoking bears a strong etiological association with many neovascularization-related diseases like cancer, cardiovascular disease and macular degeneration. Although cigarette smoke is a complex mixture of many compounds, nicotine is the major active and addictive component of tobacco. Recent studies have shown that nicotine can enhance angiogenesis and arteriogenesis in several experimental systems and animal models. The pro-angiogenic activity of nicotine is mediated by nicotinic acetylcholine receptors, which have been found to be expressed on several types of cells in the vasculature like endothelial cells, smooth muscle cells and immune cells. The present review summarizes the pro-angiogenic activity of nicotine in neoplastic and non-neoplastic disease. The present article focuses on the role of nAChRs particularly alpha 7-nAChR in mediating the pro-angiogenic effects of nicotine. The expression patterns of nAChRs on various components of the vasculature are discussed. The complex signaling pathways underlying the angiogenic effect of nAChRs are described. The review also takes a look at the therapeutic potential of nAChR agonists and antagonists in angiogenesis-related diseases. More basic research as well as patient-oriented clinical studies is needed to firmly establish the clinical potential of nAChR ligands in angiogenesis-based therapies. Also the side effects of targeting nAChRs remain to be established in patients. The development of selective nAChR agonists and antagonists with improved specificity may represent novel therapeutic regimens in the treatment of angiogenesis-related diseases. (c) 2008 Elsevier Inc. All rights reserved,