TY - JOUR
T1 - Nicotine and pathological angiogenesis
AU - Lee, Jieun
AU - Cooke, John P.
N1 - Funding Information:
This work was supported in part by grants from the National Institutes of Health ( RC2HL103400 , 1U01HL100397 and K12 HL087746 ), and by the Tobacco Related Disease Research Program of the University of California ( 18XT-0098 and 18FT-0064 ). Dr. Cooke is an inventor on Stanford University patents related to therapeutic modulation of angiogenesis by agonists or inhibitors of the nACh receptors.
PY - 2012/11/27
Y1 - 2012/11/27
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Atherosclerosis
KW - Choroidal neovascularization
KW - nAChR (nicotinic acetylcholine receptor)
KW - Nicotine
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U2 - 10.1016/j.lfs.2012.06.032
DO - 10.1016/j.lfs.2012.06.032
M3 - Article
C2 - 22796717
AN - SCOPUS:84872810584
SN - 0024-3205
VL - 91
SP - 1058
EP - 1064
JO - Life sciences
JF - Life sciences
IS - 21-22
ER -