Mechanisms of enhanced production of PGI(2) in cultured rat vascular smooth muscle cells enriched with eicosapentaenoic acid

The present investigation was performed to clarify the effect of EPA on PGI(2) 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 PGI(2) 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 A(2) nor PGI(2) 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 PGI(2) 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 PGI(2) production. Although EPA increased PGI(2) production, only a negligible amount of PGI(3) was produced by rat aortic tissues. Enhanced production of PGI(2) might contribute to the anti-atherogenic effect of EPA. (C) 1997 Elsevier Science Ireland Ltd.