title: Mechanisms of enhanced production of PGI2 in cultured rat vascular smooth muscle cells enriched with eicosapentaenoic acid.
abstract: The present investigation was performed to clarify the effect of EPA on PGI2 production in vitro using cultured rat vascular smooth muscle cells (VSMC). To simulate in vivo conditions, a triacylglycerol (TG) emulsified form of EPA was used. An increase in EPA content was achieved without alteration of arachidonic acid concentration. These experiments clearly demonstrated that co-incubation of EPA-TG increased PGI2 production by cultured VSMC in a dose dependent fashion. Among polyunsaturated fatty acid TG examined (docosahexaenoic acid, linoleic acid, oleic acid and EPA), only EPA-TG was effective. Cyclooxygenase (COX) was activated, but neither phospholipase A2 nor PGI2 synthase activity was changed. EPA treatment did not alter the amount of COX-1 and COX-2 protein in VSMC. Addition of antioxidants, such as butylated hydroxytoluene or vitamin E, decreased MDA levels in the medium and cells and reversed the enhanced PGI2 production in EPA rich-VSMC. Therefore, the high polyunsaturation of EPA could generate low levels of lipid peroxides and thereby lead to activation of COX and an increased PGI2 production. Although EPA increased PGI2 production, only a negligible amount of PGI3 was produced by rat aortic tissues. Enhanced production of PGI2 might contribute to the anti-atherogenic effect of EPA.
authors.affiliation: The Second Department of Internal Medicine, Chiba University School of Medicine, Chuo-Ku, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Terano
authors.forename: A
authors.initials: A
authors.lastname: Hirai
authors.forename: T
authors.initials: T
authors.lastname: Shiina
authors.forename: Y
authors.initials: Y
authors.lastname: Tamura
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000166:cytology; D015153:Blotting, Western; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects; D002855:Chromatography, Thin Layer; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010544:Peroxidases / Q000187:drug effects / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013050:Spectrometry, Fluorescence; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007527:Isoenzymes; D008054:Lipid Peroxides; D008565:Membrane Proteins; D014280:Triglycerides; C051339:1,2,3-trieicosapentaenoyl glycerol; D015118:Eicosapentaenoic Acid; D011464:Epoprostenol; D010544:Peroxidases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat