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Angiopoeitin-2 modulates Survivin expression in OxLDL-induced endothelial cell apoptosis
Rongsong Li1, David Mittelstein, Karen Fang
1Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, United States.
Abstract:
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 microg/ml of OxLDL down-regulated Ang-2 expression as early as 4h after treatment and persisted up to 24h (p<0.05, n=3), but did not down-regulate Survivin until the 24h 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.
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