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Angiopoietin-1(Ang-1) is a vasculogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. We examined the effect of angiopoietin-1(Ang-1) on radiation-induced apoptosis in human umbilical vein endothelial cells(HUVECS) and receptor/second messenger signal transduction pathway for Ang-1’s effect on HUVECs. The percent of apoptotic cells under control condition(0Gy) was . Irradiation induced apoptosis was increased in a dose(1, 5, 10, and 15Gy)- and time 12, 24, 48 and 72hr)-dependent manner. The percent of apoptotic cells was approximately after 15 Gy of irradiation. Under these conditions, pretreatment with Ang-1’s (50, 100, 200, and 400 ng/ml) inhibited irradiation-induced apoptosis in human umbilical vein endothelial cells in a dose-dependent manner. Two hundred ng/ml of Ang-1 inhibited approximately of the apoptotic events that occurred in the 10 Gy-irradiated cells. Pre-treatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the Ang-1’s antiapoptotic effects. Phosphatidylinositol 3’-kinase (P13-kinase) specific inhibitor, wortmanin and LY294002, blocked the Ang-1-induced antiapoptotic effect. Ang-1 promotes the survival of endothelial cells in irradiation-induced apoptosis through Tie2 receptor binding and P13-kinase activation. Pretreatment of Ang-1 could be beneficial in maintaining normal endothelial cell integrity during irradiation therapy.
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