Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42/p44 mitogen‐activated protein kinase
Open Access
- 22 December 1997
- journal article
- Published by Wiley in FEBS Letters
- Vol. 420 (1) , 28-32
- https://doi.org/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 (PlGF), 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.Keywords
This publication has 33 references indexed in Scilit:
- VEGF Gene Transfer Reduces Intimal Thickening via Increased Production of Nitric Oxide in Carotid ArteriesHuman Gene Therapy, 1997
- Mechanisms of angiogenesisNature, 1997
- The Vascular Endothelial Growth Factor Receptor Flt-1 Mediates Biological ActivitiesJournal of Biological Chemistry, 1996
- Inhibition of MAP kinase kinase (MEK) blocks endothelial PGI2 release but has no effect on von Willebrand factor secretion or E‐selectin expressionFEBS Letters, 1996
- Cytosolic Phospholipase A2 Is Phosphorylated in Collagen- and Thrombin-stimulated Human Platelets Independent of Protein Kinase C and Mitogen-activated Protein KinasePublished by Elsevier ,1995
- Hypoxia and platelet‐derived growth factor‐BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cellsFEBS Letters, 1995
- The pathogenesis of atherosclerosis: a perspective for the 1990sNature, 1993
- cPLA2 is phosphorylated and activated by MAP kinaseCell, 1993
- The fms -Like Tyrosine Kinase, a Receptor for Vascular Endothelial Growth FactorScience, 1992
- A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAPCell, 1991