Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway

A productive angiogenic response must couple to the survival machinery of e ndothelial cells to preserve the integrity of newly formed vessels. Angiopo ietin-1 (Ang-l) is an endothelium-specific ligand essential for embryonic v ascular stabilization, branching morphogenesis, and post-natal angiogenesis , but its contribution to endothelial cell survival has not been completely elucidated. Here we show that Ang-l acting via the Tie 2 receptor induces phosphorylation of the survival serine-threonine kinase, Akt (or protein ki nase B). This is associated with up-regulation of the apoptosis inhibitor, survivin, in endothelial cells and protection of endothelium from death-ind ucing stimuli. Moreover, dominant negative survivin negates the ability of Ang-l to protect cells from undergoing apoptosis, The activation of antiapo ptotic pathways mediated by Akt and survivin in endothelial cells may contr ibute to Ang-l stabilization of vascular structures during angiogenesis, in vivo.