Mechanisms of enhanced production of PGI2 in cultured rat vascular smooth muscle cells enriched with eicosapentaenoic acid.
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.
Saito
J
J
The Second Department of Internal Medicine, Chiba University School of Medicine, Chuo-Ku, Japan.
Terano
T
T
Hirai
A
A
Shiina
T
T
Tamura
Y
Y
Saito
Y
Y
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
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