Vascular Endothelial Growth Factor (VEGF) Induces Plasminogen Activators and Plasminogen Activator inhibitor-1 in Microvascular Endothelial Cells

Biochem Biophys Res Commun. 1991 Dec 16;181(2):902-6. doi: 10.1016/0006-291x(91)91276-i.

Abstract

Extracellular proteolysis is believed to be an essential component of the angiogenic process. The effects of VEGF, a recently described angiogenic factor, were assessed on PA activity and PA and PAI-1 mRNA levels in microvascular endothelial cells. u-PA and t-PA activity were increased by VEGF in a dose-dependent manner, with maximal induction at 30 ng/ml. u-PA and t-PA mRNAs were increased 7.5- and 8-fold respectively after 15 hours, and PAI-1 mRNA 4.5-fold after 4 hours exposure to VEGF. At equimolar concentrations (0.5 nM), VEGF was a more potent inducer of t-PA mRNA than bFGF, while bFGF was a more potent inducer of u-PA and PAI-1 mRNAs. In addition, VEGF induced u-PA and PAI-1 mRNAs with kinetics similar to those previously demonstrated for bFGF. These results demonstrate the regulation of PA and PAI-1 production by VEGF in microvascular endothelial cells and are in accord with the hypothesis that extracellular proteolysis, appropriately balanced by protease inhibitors, is required for normal capillary morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Endothelial Growth Factors / pharmacology*
  • Endothelium, Vascular / metabolism*
  • Humans
  • Lymphokines / pharmacology*
  • Microcirculation
  • Plasminogen Activators / biosynthesis*
  • Plasminogen Activators / genetics
  • Plasminogen Inactivators / metabolism*
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Tissue Plasminogen Activator / biosynthesis
  • Tissue Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / genetics
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Plasminogen Inactivators
  • RNA, Messenger
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Plasminogen Activators
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator