Angiogenesis modulation by nicotine and nicotinic ligands

Shaker A. Mousa, Hugor Arias

Research output: Contribution to journalArticlepeer-review

Abstract

Nicotine, one of the thousands of chemicals in cigarette smoke has a highly debated effect on cell proliferation and tissue healing. Recent studies documented its pro-angiogenesis effects by stimulating endothelial cell α7 non-neronal nicotinic acetylcholine receptors (α7 AChR). Angiogenesis is a critical physiological process for cell survival and development. Endothelial cells, necessary for the course of angiogenesis, express several non-neuronal AChRs. The most important functional non-neuronal AChRs are homomeric α7 AChRs and several heteromeric AChRs formed by a combination of α3, α5, β2, and β4 subunits, including α3β4-containing AChRs. In endothelial cells, α7 AChR stimulation indirectly triggers the activation of the integrin ανβ 3 receptor and an intracellular MAP kinase (ERK) pathway that mediates angiogenesis. Non-selective cholinergic agonists such as nicotine have been shown to induce angiogenesis, enhancing tumor progression. Moreover, α7 AChR selective antagonists such as α-bungarotoxin and methyllycaconitine as well as the nonspecific antagonist mecamylamine have been shown to inhibit endothelial cell proliferation and ultimately blood vessel formation. Exploitation of such pharmacologic properties can lead to the discovery of new specific cholinergic antagonists as anti-cancer therapies. Conversely, the pro-angiogenic effect elicited by specific agonists can be used to treat diseases that respond to re-vascularization such as diabetic ischemia and atherosclerosis, as well as to accelerate wound healing. In this review we discuss the pharmacological evidence supporting the importance of non-neuronal AChRs in angiogenesis and potential intracellular mechanisms by which α7 AChR activation mediates these cellular processes.

Original languageEnglish
Pages (from-to)91-104
Number of pages14
JournalJournal of Pediatric Biochemistry
Volume1
Issue number2
DOIs
StatePublished - 1 Jan 2010
Externally publishedYes

Keywords

  • Angiogenesis
  • growth factors
  • intracellular pathways
  • nicotinic agonists
  • nicotinic antagonists
  • non-neuronal nicotinic receptors
  • wound healing

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