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Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A 2 in endothelial cells via p42/p44 mitogen‐activated protein kinase
Author(s) -
Wheeler-Jones Caroline,
Abu-Ghazaleh Robin,
Cospedal Rosario,
Houliston Rebecca A,
Martin John,
Zachary Ian
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01481-6
Subject(s) - arachidonic acid , vascular endothelial growth factor , mitogen activated protein kinase , prostacyclin , medicine , endocrinology , protein kinase a , kinase , phospholipase a2 , vascular endothelial growth factor a , protein kinase c , chemistry , biology , microbiology and biotechnology , biochemistry , vegf receptors , enzyme
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 (PlGF), 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.