Regulation of prostaglandin synthesis in human vascular cells.
Prostacyclin (PGI2) synthesis in human vascular tissue is mainly regulated by the activity of enzymes that metabolize arachidonic acid, and especially by the activity of cyclooxygenase. The activity of this enzyme depends upon the balance between its synthesis and its inactivation by peroxidated metabolites or drugs. Cyclooxygenase in vascular endothelial cells is strongly inhibited by aspirin, but is rapidly resynthesized. The resynthesis proceeds more rapidly in endothelium than in smooth muscle cells. Growth factors for vascular cells strongly influence cyclooxygenase production and activity. PDGF both releases arachidonate and stimulates cyclooxygenase synthesis in fibroblasts and smooth muscle cells, and ECGF enhances new enzyme synthesis. By contrast, we find that the endothelial growth factor depresses PGI2 synthesis in human endothelial cells in a time and concentration-dependent manner. This inhibitory effect is potentiated by heparin. The inhibition correlates with a decrease in the content of immunoreactive cyclooxygenase within the endothelial cells when they are grown in the presence of ECGF and heparin. These findings suggest that proliferation selectively suppresses the function of prostaglandin synthesis in endothelial cells.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011464:Epoprostenol / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D013268:Stimulation, Chemical; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D010982:Platelet-Derived Growth Factor; D016718:Arachidonic Acid; D005346:Fibroblast Growth Factors; D006493:Heparin; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D013917:Thrombin; D001241:Aspirin