Papapetropoulos A, Fulton D, Mahboubi K, Kalb R G, O'Connor D S, Li F, Altieri D C, Sessa W C
Department of Pharmacology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
J Biol Chem. 2000 Mar 31;275(13):9102-5. doi: 10.1074/jbc.275.13.9102.
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.
有效的血管生成反应必须与内皮细胞的存活机制相结合，以维持新形成血管的完整性。血管生成素-1（Ang-1）是一种内皮细胞特异性配体，对胚胎血管稳定、分支形态发生和出生后血管生成至关重要，但其对内皮细胞存活的贡献尚未完全阐明。在此我们表明，通过Tie 2受体起作用的Ang-1可诱导存活丝氨酸-苏氨酸激酶Akt（或蛋白激酶B）磷酸化。这与内皮细胞中凋亡抑制剂survivin的上调以及内皮细胞免受死亡诱导刺激的保护相关。此外，显性负性survivin消除了Ang-1保护细胞免于凋亡的能力。内皮细胞中由Akt和survivin介导的抗凋亡途径的激活可能有助于体内血管生成过程中Ang-1对血管结构的稳定作用。
