Hypoxia-inducible factor-1alpha induces cell cycle arrest of endothelial cells

BACKGROUND: Hypoxia can induce tissue injury, including apoptosis of endothelial cells. However, little is known about the effects of hypoxia on endothelial cell function. We assessed the effects of hypoxia inducible factor (HIF)-1alpha on the functional characteristics of endothelial cells, particularly on cell cycle regulators, by cationic liposome-mediated transfection of HIF-1alpha-expression vector into the cells. RESULTS: Transfection of the HIF-1alpha gene in endothelial cells resulted in (a) reduced proliferation and detachment of the cells; (b) up-regulation of intracellular p21waf1/cip1 and down-regulation of bcl-2; (c) reduced activities of cyclin-dependent kinase (CDK)-4 and CDK-6; (d) cell cycle arrest at G0/G1 phase; and (e) apoptosis of the cells. CONCLUSIONS: HIF-1alpha can induce cell cycle arrest, resulting in the reduced proliferation and apoptosis of endothelial cells, and the hypoxia-induced cell death may be involved by suppression of anti-apoptotic molecule, bcl-2.