Cholinergic modulation of angiogenesis: Role of the 7 nicotinic acetylcholine receptor

Jenny C.F. Wu, Andrzej Chruscinski, Vinicio A. De Jesus Perez, Harvir Singh, Maria Pitsiouni, Marlene Rabinovitch, Paul J. Utz, John P. Cooke

Research output: Contribution to journalArticle

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)433-446
Number of pages14
JournalJournal of Cellular Biochemistry
Volume108
Issue number2
DOIs
StatePublished - Oct 1 2009

Keywords

  • nAChR
  • RPP
  • siRNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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