Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42/p44 mitogen-activated protein kinase

FEBS Lett. 1997 Dec 22;420(1):28-32. doi: 10.1016/s0014-5793(97)01481-6.

Abstract

Vascular endothelial growth factor (VEGF) stimulated a time- and concentration-dependent increase in PGI2 synthesis in human umbilical vein endothelial cells with a mean maximum increase of 2-fold above basal levels at 25 ng/ml after 60 min. VEGF also rapidly stimulated the release of arachidonic acid and phosphorylation and activation of cytosolic phospholipase A2 (cPLA2). The VEGF-related factor, placenta growth factor (PIGF), had little effect on PGI2 synthesis, arachidonic acid release or cPLA2 activation. PD98059, a selective inhibitor of MAP kinase kinase, caused complete inhibition of VEGF-stimulated MAP kinase activity, PGI2 synthesis and cPLA2 gel retardation, but had no effect on VEGF-induced vWF secretion. These findings provide the first evidence that VEGF can stimulate PGI2 synthesis via cPLA2-mediated arachidonic acid release and indicate that VEGF stimulation of this biosynthetic pathway may occur, at least in part, via activation of p42/p44 MAP kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cells, Cultured
  • Cytosol / enzymology
  • Endothelial Growth Factors / pharmacology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Epoprostenol / biosynthesis*
  • Flavonoids / pharmacology
  • Humans
  • Lymphokines / pharmacology*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases*
  • Molecular Weight
  • Phospholipases A / chemistry
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Protein Kinase Inhibitors
  • Signal Transduction / physiology
  • Umbilical Veins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Enzyme Inhibitors
  • Flavonoids
  • Lymphokines
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Arachidonic Acid
  • Epoprostenol
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Phospholipases A
  • Phospholipases A2
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one