Angiopoeitin-2 (Ang-2) antagonizes Angiopeitin-1 (Ang-1)-mediated Tie-2 signaling. Ang-1 is reported to up-regulate anti-apoptotic Survivin expression. Here, we investigated the interplay between Ang-2 and Survivin in response to oxidized low density lipoprotein (OxLDL)-induced apoptosis. We demonstrate that treatment of human aortic endothelial cells (HAEC) with 100 mu g/ml of OxLDL down-regulated Ang-2 expression as early as 4 h after treatment and persisted up to 24 h (p < 0.05, n = 3), but did not down-regulate Survivin until the 24 h point. Further, treatment of HAEC with recombinant Ang-2 up-regulated Survivin expression (at Ang-2 >= 200 ng/ml, p < 0.05, n = 3) and attenuated the OxLDL-mediated down-regulation of Survivin (p < 0.05, n = 3). Knockdown of Ang-2 further down-regulated Survivin expression, whereas over-expression of Survivin attenuated OxLDL-induced HAEC apoptosis (p < 0.05, n = 3). Hence, Ang-2 mediated Survivin expression in response to OxLDL-induced endothelial apoptosis. (C) 2011 Elsevier Inc. All rights reserved.