Angiogenesis and the role of the endothelial nicotinic acetylcholine receptor

Abstract

An endothelial nicotinic acetycholine receptor (nAChR) mediates endothelial proliferation, survival, migration and tube formation in vitro, and angiogenesis in vivo. Exogenous nicotine stimulates this angiogenic pathway. This action of nicotine may contribute to tumor angiogenesis and tumor growth; atherosclerotic plaque neovascularization and progression; and other tobacco-related diseases. The endothelial nAChR mediates an angiogenic pathway that is interdependent with growth factor mediated pathways, as shown by pharmacological and molecular studies. The characterization of this new angiogenic pathway may provide a new therapeutic avenue for disorders of insufficient or pathological angiogenesis.

Fig 1

Histogram showing average counts of migrating cells in wounded endothelial monolayer model. The endothelial cell (EC) migration assay begins with a confluent EC monolayer which is injured by scraping away half of the cells (see insert). EC migrating into the denuded region (ie. across the dashed line, see insert), are counted. Angiogenic agents accelerate this migration. In this experiment we have treated EC with vehicle or growth factors, in the presence or absence of neostigmine (NEO), a cholinesterase inhibitor. In this histogram, the number of migrating cells are expressed as a percentage of the number of EC migrating under unstimulated conditions. VEGF (1 ng/ml; black bar) increases EC migration to the same degree as FGF or Nicotine; high dose VEGF (10ng/ml) gives the greatest response. Neostigmine (NEO) increases EC migration over 50%, a similar effect as that with nicotine, FGF or low dose VEGF. The combination of neostigmine and low dose VEGF (3^rd black bar) gives a greater response than high dose VEGF.