Angiopoietin-1 Inhibits Endothelial Cell Apoptosis via the Akt/Survivin Pathway*
By A. Papapetropoulos, David Fulton, K. Mahboubi, R. Kalb, Daniel S. O'Connor, Fengzhi Li, D. Altieri, W. Sessa. Journal of Biological Chemistry, 2000
691 citations recorded by the source corpus.
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.
Subfields: Cardiology and Cardiovascular Medicine, Immunology and Allergy, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/bf3cadccc41fdde954458049092e6de1474792b3
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Citations in the corpus
- Angiogenesis in wound repair: Angiogenic growth factors and the extracellular matrix (2003, background): “Ang-1 protects endothelial cells from apoptosis through PI3 kinase/Akt-dependent pathway and facilitates endothelial cell survival (Papapetropoulos et al., 2000).”
- Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. (2006, background): “Tie2, when activated by its ligand, Angiopoietin-1, signals through PI3K to regulate vascular development (Kim et al., 2000; Papapetropoulos et al., 2000).”
- The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. (2004, background): “Ang-1 acts as the Tie-2 stimulating cytokine thereby positively controlling endothelial cell survival and vessel maturation which is associated with the quiescent non-proliferating endothelial cell phenotype.(5,33) The functions of Ang-2 appear to be more complex and Ang-2 can probably act in a cont”
- Survivin, versatile modulation of cell division and apoptosis in cancer (2003, background): “…denominator of this pathway is the requirement for PI3-kinase/Akt activation, a general antiapoptotic signal (Datta et al., 1999) that has been implicated in the upregulation of survivin induced by GM-CSF, CSF and Ang-1 (Papapetropoulos et al., 2000; Carter et al., 2001; Fukuda et al., 2002).”