title: Angiopoeitin-2 modulates Survivin expression in OxLDL-induced endothelial cell apoptosis.
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 μg/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.
authors.affiliation: Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, United States.
authors.forename: Rongsong
authors.initials: R
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Mittelstein
authors.forename: Karen
authors.initials: K
authors.lastname: Fang
authors.forename: Tyler
authors.initials: T
authors.lastname: Beebe
authors.forename: Katherine
authors.initials: K
authors.lastname: Quigley
authors.forename: Judith
authors.initials: J
authors.lastname: Berliner
authors.forename: Tzung K
authors.initials: TK
authors.lastname: Hsiai
mesh_terms: D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D000077022:Survivin
chemical_list: D042702:Angiopoietin-2; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008077:Lipoproteins, LDL; D000077022:Survivin; C099252:oxidized low density lipoprotein