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

FEBS Letters

Abu-Ghazaleh, Robin¹  Zachary, Ian¹  Wheeler-Jones, Caroline²  Martin, John¹  Cospedal, Rosario¹  Houliston, Rebecca A² 

[1] Cruciform Project and Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK;Vascular Biology Research Centre, King's College London, Campden Hill Road, Kensington, London W8 7AH, UK

关键词: Thrombin;    Signal transduction;    Endothelium;    Arachidonic acid;    Von Willebrand factor;    BSA;    bovine serum albumin;    DMEM;    Dulbecco's modified Eagle's medium;    FCS;    fetal calf serum;    HUVEC;    human umbilical vein endothelial cells;    IgG;    immunoglobulin G;    MAP kinase;    mitogen-activated protein kinase;    mAb;    monoclonal antibody;    PBS;    phosphate-buffered saline;    PGI2;    prostacyclin;    cPLA2;    cytosolic phospholipase A2;    PlGF;    placenta growth factor;    SDS-PAGE;    sodium dodecyl sulphate-polyacrylamide gel electrophoresis;    VEGF;    vascular endothelial growth factor;    vWF;    von Willebrand factor;    VSMC;    vascular smooth muscle cells;   

DOI  :  10.1016/S0014-5793(97)01481-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown