Mechanisms of enhanced production of PGI2 in cultured rat vascular smooth muscle cells enriched with eicosapentaenoic acid

• Published in: Atherosclerosis Vol. 131; no. 2; pp. 219 - 228
• Main Authors: SAITO, J, TERANO, T, HIRAI, A, SHIINA, T, TAMURA, Y, SAITOI, Y
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.06.1997
• Subjects: Animals; Antioxidants - pharmacology; Aorta, Thoracic - cytology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blotting, Western; Cardiology. Vascular system; Cell Division; Cells, Cultured - drug effects; Chromatography, Thin Layer; Cyclooxygenase 1; Cyclooxygenase 2; Dose-Response Relationship, Drug; Eicosapentaenoic Acid - pharmacology; Epoprostenol - biosynthesis; Isoenzymes - drug effects; Isoenzymes - metabolism; Lipid Peroxides - biosynthesis; Medical sciences; Membrane Proteins; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Peroxidases - drug effects; Peroxidases - metabolism; Prostaglandin-Endoperoxide Synthases - drug effects; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Inbred WKY; Spectrometry, Fluorescence; Triglycerides - metabolism; Cell culture; Prostaglandin I2; Prostaglandin; Rat; Arachidonic acid derivatives; Rodentia; Polyunsaturated fatty acid; Cardiovascular disease; Smooth muscle; Fatty acids; In vitro; Vascular disease; Vertebrata; Mammalia; Animal; Atherosclerosis; Aorta; Mechanism of action; Vascular wall; Eicosapentaenoic acid; Protection
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(97)00048-8

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.