Alpha-7 nicotinic acetylcholine receptor (CHRNA7) (alpha7-nAChR)

The Alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is a homopentameric ligand-gated ion channel that is significantly expressed in vascular endothelial cells, where it serves as a key regulator of non-neuronal cholinergic signaling (UniProt P36544). In the endothelium, activation of alpha7-nAChR by acetylcholine or exogenous agonists like nicotine stimulates angiogenesis by promoting cell proliferation, migration, and tube formation through the activation of the PI3K/Akt and MAPK/ERK pathways (Heeschen et al., 2002). Beyond its role in vascular growth, this receptor is a central component of the cholinergic anti-inflammatory pathway, where its activation on macrophages and endothelial cells inhibits the production of pro-inflammatory cytokines (Wang et al., 2003). In pathological contexts, overstimulation of endothelial alpha7-nAChR contributes to tumor vascularization and atherosclerosis, while its impairment is linked to poor wound healing and peripheral artery disease (Cooke, 2007). Consequently, alpha7-nAChR is a target for both pro-angiogenic therapies in ischemic disease and anti-angiogenic strategies in oncology.

Other names

CHRNA7Alpha-7 nicotinic receptorEndothelial nicotinic acetylcholine receptorNon-neuronal nicotinic acetylcholine receptorCholinergic receptor nicotinic alpha 7 subunit

Agonism of the alpha7-nAChR on endothelial cells triggers calcium-dependent signaling pathways, including PI3K/Akt, MAPK/ERK, and JAK2/STAT3, which enhance endothelial cell survival, migration, and the expression of pro-angiogenic factors like VEGF (Heeschen et al., 2002; Cooke, 2007). Conversely, its activation in the context of inflammation leads to the inhibition of NF-kappaB translocation, reducing the release of pro-inflammatory cytokines (Wang et al., 2003).