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

Vascular endothelial growth factor (VEGF) stimulated a time-and concentration-dependent increase in PGI(2) 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 A(2) (cPLA(2)), The VEGF-related factor, placenta growth factor (PICF), had little effect on PGI(2) synthesis, arachidonic acid release or cPLA(2) activation, PD98059, a selective inhibitor of MAP kinase kinase, caused complete inhibition of VEGF-stimulated MAP kinase activity, PGI(2) synthesis and cPLA(2) gel retardation, but had no effect on VEGF-induced vWF secretion, These findings provide the first evidence that VEGF can stimulate PGI(2) synthesis via cPLA(2)-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. (C) 1997 Federation of European Biochemical Societies.