Angiopoietin-1 inhibits irradiation- and mannitol-induced apoptosis in endothelial cells

Background and Purpose - Angiopoietin-1 (Ang1) is a vasculogenic factor tha t signals through the endothelial cell-specific Tie2 receptor tyrosine kina se. We recently reported that Ang1 prevented apoptosis induced by serum dep rivation in endothelial cells. In this study, we examined whether Ang1 prev ents apoptosis in endothelial cells treated with irradiation or clinical co ncentrations of mannitol. Methods and Results - Ang1 prevented irradiation- and mannitol-induced apop tosis in human umbilical vein endothelial cells in a dose-dependent manner. Pretreatment with soluble Tie2 receptor, but not Tie1 receptor, blocked th e antiapoptotic effect of Ang1. Two phosphatidylinositol 3'-kinase (PI3-kin ase)-specific inhibitors, wortmannin and LY294002, blocked the Ang1-induced antiapoptotic effect. The antiapoptotic potency of Ang1 was similar to or greater than that of vascular endothelial growth factor, basic fibroblast g rowth factor, and endothelin-1. Ang1 also prevented apoptosis in cultured e ndothelial cells from porcine pulmonary and coronary arteries and in endoth elial cells of explanted rat aorta. Conclusions - Ang1 promotes the survival of endothelial cells in irradiatio n- and mannitol-induced apoptosis through Tie2 receptor binding and PI3-kin ase activation. Pretreatment with Ang1 could be beneficial in maintaining n ormal endothelial cell integrity during intracoronary irradiation or system ic mannitol therapy.