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

Andreas Papapetropoulos, David Fulton, Keyvan Mahboubi, Robert G. Kalb, Daniel S. O'Connor, Fengzhi Li, Dario C. Altieri, William C. Sessa

Research output: Contribution to journalArticlepeer-review

534 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)9102-9105
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number13
DOIs
StatePublished - Mar 31 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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