Hypoxia‐inducible factor‐1α induces cell cycle arrest of endothelial cells

Abstract

Abstract 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)‐1α on the functional characteristics of endothelial cells, particularly on cell cycle regulators, by cationic liposome‐mediated transfection of HIF‐1α‐expression vector into the cells. Results: Transfection of the HIF‐1α gene in endothelial cells resulted in (a) reduced proliferation and detachment of the cells; (b) up‐regulation of intracellular p21 waf1/cip1 and down‐regulation of bcl‐2; (c) reduced activities of cyclin‐dependent kinase (CDK)‐4 and CDK‐6; (d) cell cycle arrest at G 0 /G 1 phase; and (e) apoptosis of the cells. Conclusions: HIF‐1α 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.