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 language | English |
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Title of host publication | Angiogenesis Modulations in Health and Disease |
Subtitle of host publication | Practical Applications of Pro- and Anti-angiogenesis Targets |
Publisher | Springer Netherlands |
Pages | 55-75 |
Number of pages | 21 |
ISBN (Electronic) | 9789400764675 |
ISBN (Print) | 9400764669, 9789400764668 |
DOIs | |
State | Published - 1 Nov 2013 |
Externally published | Yes |