Apoptosis inducers endotoxin and Fas-ligation enhance the expression of vascular endothelial growth factor in human endothelial cells

Endothelium. 1999;6(4):335-40. doi: 10.3109/10623329909078500.

Abstract

Endothelial cells in culture were exposed during four hours to the apoptosis inducing agents endotoxin (lipopolysaccharide, LPS) and Fas-ligand mimicking antibody in various concentrations. With addition of a deletion primer as internal standard a competitive RT-PCR was performed to measure semi-quantitatively the expression of mRNA of Vascular endothelial growth factor (VEGF). It appeared that endothelial cells survive increasing amounts of LPS and show a concentration- and time-dependent increase in the expression of VEGF-mRNA. The same effect was found with Fas-ligation, although at high concentrations Fas-ligation induced no further increase, but even a decrease of VEGF expression, possibly related to cell damage. Apoptotic cells were rarely observed after LPS-stimulation, but simultaneous incubation with a blocking antibody to VEGF resulted in a significant increase in apoptosis. We hypothesize that endothelial cells are resistant to apoptosis induction by autocrine expression of VEGF under stress conditions.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cells, Cultured
  • DNA Primers / chemistry
  • Dose-Response Relationship, Drug
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Humans
  • In Situ Nick-End Labeling
  • Lipopolysaccharides / pharmacology*
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • fas Receptor / pharmacology*

Substances

  • DNA Primers
  • Endothelial Growth Factors
  • Lipopolysaccharides
  • Lymphokines
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • fas Receptor