Role of non-neuronal nicotinic acetylcholine receptors in angiogenesis modulation

Shaker A. Mousa, Hugo R. Arias, Paul J. Davis

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Angiogenesis is a critical physiological process for cell survival and development. Endothelial cells, necessary for the course of angiogenesis, express several non-neuronal nicotinic acetylcholine receptors (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 αvβ3 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 revascularization such as diabetic ischemia and foot ulcer, as well as to accelerate wound-healing. In this chapter we discuss the pharmacological evidence supporting the importance of non-neuronal AChRs in angiogenesis. We also explore potential intracellular mechanisms by which α7 AChR activation mediates this vital cellular process.

Original languageEnglish
Title of host publicationAngiogenesis Modulations in Health and Disease
Subtitle of host publicationPractical Applications of Pro- and Anti-angiogenesis Targets
PublisherSpringer Netherlands
Pages55-75
Number of pages21
ISBN (Electronic)9789400764675
ISBN (Print)9400764669, 9789400764668
DOIs
Publication statusPublished - 1 Nov 2013
Externally publishedYes

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Mousa, S. A., Arias, H. R., & Davis, P. J. (2013). Role of non-neuronal nicotinic acetylcholine receptors in angiogenesis modulation. In Angiogenesis Modulations in Health and Disease: Practical Applications of Pro- and Anti-angiogenesis Targets (pp. 55-75). Springer Netherlands. https://doi.org/10.1007/978-94-007-6467-5_6