Cholinergic modulation of angiogenesis: Role of the 7 nicotinic acetylcholine receptor |
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Authors: | Jenny C.F. Wu Andrzej Chruscinski Vinicio A. De Jesus Perez Harvir Singh Maria Pitsiouni Marlene Rabinovitch Paul J. Utz John P. Cooke |
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Affiliation: | 1. Department of Cardiovascular Medicine, Stanford University, Stanford, California 94305;2. Department of Immunology, Stanford University, Stanford, California 94305;3. Department of Medicine, Stanford University, Stanford, California 94305 |
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Abstract: | Pathological angiogenesis contributes to tobacco‐related diseases such as malignancy, atherosclerosis and age‐related macular degeneration. Nicotine acts on endothelial nicotinic acetylcholine receptors (nAChRs) to activate endothelial cells and to augment pathological angiogenesis. In the current study, we studied nAChR subunits involved in these actions. We detected mRNA for all mammalian nAChR subunits except α2, α4, γ, and δ in four different types of ECs. Using siRNA methodology, we found that the α7 nAChR plays a dominant role in nicotine‐induced cell signaling (assessed by intracellular calcium and NO imaging, and studies of protein expression and phosphorylation), as well as nicotine‐activated EC functions (proliferation, survival, migration, and tube formation). The α9 and α7 nAChRs have opposing effects on nicotine‐induced cell proliferation and survival. Our studies reveal a critical role for the α7 nAChR in mediating the effects of nicotine on the endothelium. Other subunits play a modulatory role. These findings may have therapeutic implications for diseases characterized by pathological angiogenesis. J. Cell. Biochem. 108: 433–446, 2009. © 2009 Wiley‐Liss, Inc. |
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Keywords: | nAChR siRNA RPP |
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