Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: balance between growth and death signals

J Mol Cell Cardiol. 1997 May;29(5):1321-30. doi: 10.1006/jmcc.1996.0365.


A series of experiments was performed to determine whether vascular endothelial growth factor (VEGF), in addition to its endothelial cell specific mitogenic activity, can also protect endothelial cells from toxin-induced programmed cell death. Apoptosis was induced in endothelial cell culture with tumor necrosis factor-alpha (TNF-alpha). Simultaneous exposure of endothelial cells to VEGF resulted in a dose dependent inhibition of apoptosis when evaluated by: (1) direct counting of cells with morphologic features of apoptosis after acridine orange staining; (2) analysis of DNA fragmentation by (a) agarose gel electrophoresis and (b) fluorescence activated cell sorting (FACS); and (3) viability assays dependent upon mitochondrial function. Induction of fibronectin and beta 3 integrin expression in endothelial cells by VEGF suggests that altered adhesion molecule expression may explain this survival effect.

MeSH terms

  • Animals
  • Apoptosis*
  • Blotting, Northern
  • Cattle
  • Cell Line
  • Cell Survival
  • Cells, Cultured
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Electrophoresis, Agar Gel
  • Endothelial Growth Factors / pharmacology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Flow Cytometry
  • Humans
  • Lymphokines / pharmacology*
  • Microscopy, Fluorescence
  • Mitogens / pharmacology*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Mitogens
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors