Nicotine and pathological angiogenesis

This paper describes the role of endothelial nicotinic acetylcholine receptors (nAChR) in diseases where pathological angiogenesis plays a role. An extensive review of the literature was performed, focusing on studies that investigated the effect of nicotine upon angiogenesis. Nicotine induces pathological angiogenesis at clinically relevant concentrations (i.e. at tissue and plasma concentrations similar to those of a light to moderate smoker). Nicotine promotes endothelial cell migration, proliferation, survival, tube formation and nitric oxide (NO) production in vitro, mimicking the effect of other angiogenic growth factors. These in vitro findings indicate that there may be an angiogenic component to the pathophysiology of major tobacco related diseases such as carcinoma, atherosclerosis, and age-related macular degeneration. Indeed, nicotine stimulates pathological angiogenesis in pre-clinical models of these disorders. Subsequently, it has been demonstrated that nicotine stimulates nAChRs on the endothelium to induce angiogenic processes, that these nAChRs are largely of the α7 homomeric type, and that there are synergistic interactions between the nAChRs and angiogenic growth factor receptors at the phosphoproteomic and genomic levels. These findings are of potential clinical relevance, and provide mechanistic insights into tobacco-related disease. Furthermore, these findings may lead to novel therapies for diseases characterized by insufficient or inappropriate angiogenesis.

Graphical abstractEndogenous acetylcholine, or exogenous nicotine, stimulates nicotinic acetylcholine receptors (nAChR) on the endothelium to initiate angiogenic processes that lead to pathological angiogenesis. Pathological angiogenesis contributes to the progression of the tobacco-related diseases of atherosclerosis, tumor, and age-related macular degeneration. Receptors for angiogenic growth factors govern pathways that share signaling elements with the nAChR and may reciprocally reinforce each other's actions. VEGFR = vascular endothelial growth factor receptor. FGFR = Fibroblast growth factor receptor.Figure optionsDownload full-size imageDownload high-quality image (59 K)Download as PowerPoint slide