Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors

Lab Invest. 1999 Feb;79(2):213-23.


Angiopoietin-1 (Ang-1) is a recently described angiogenic protein that activates the endothelial Tie 2 receptor. Disruption of the Ang-1 gene shows that it has an indispensable role in blood vessel development, but it is not clear what specific effects, if any, Ang-1 has on endothelial cell (EC) phenotypes. Here, we show that Ang-1 dose-dependently stabilizes HUVEC network organization for up to 48 hours; this action of Ang-1 is dependent on Tie-2 receptor activation, because a soluble form of the Tie2-, but not the Tie1-receptor, completely blocks the effects of Ang-1. Moreover, we show that Ang-1 potentiates the actions of other angiogenic growth factors. Ang-1 markedly increases the survival of vascular networks (up to 96 hours) exposed to either vascular endothelial growth factor or endothelial cell growth supplement, a form of acidic fibroblast growth factor. In addition, Ang-1 prevents apoptotic death in HUVEC triggered by withdrawal of endothelial cell growth supplement. Collectively, these data are consistent with the idea that Ang-1 directly acts on human EC and interacts with other angiogenic molecules to stabilize vascular structures by promoting the survival of differentiated ECs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiopoietin-1
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Collagen
  • Drug Interactions
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Gels
  • Growth Substances / pharmacology
  • Humans
  • Membrane Glycoproteins / pharmacology*
  • Neovascularization, Physiologic / physiology
  • Nitric Oxide / biosynthesis


  • ANGPT1 protein, human
  • Angiopoietin-1
  • Gels
  • Growth Substances
  • Membrane Glycoproteins
  • Nitric Oxide
  • Collagen