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

Abstract

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.