Eicosapentaenoic acid inhibits cholesteryl ester accumulation in rat peritoneal macrophages by decreasing the number of specific binding sites of acetyl LDL

Abstract

We found that rat peritoneal macrophages bind acetyl low density lipoprotein (AcLDL) by a saturable and specific manner and accumulate a substantial amount of cholesteryl ester (CE) when incubated with AcLDL. In macrophages enriched with eicosapentaenoic acid (EPA) by the ingestion of highly purified eicosapentaenoic acid-ethyl ester (EPA-E), the accumulation of CE was significantly decreased in a dose-dependent manner. In addition, the contents of EPA and docosapentaenoic acid (DPA) in macrophage phospholipids were dose dependently and significantly increased by EPA-E feeding. In contrast, the contents of arachidonic acid (AA) and docosahexaenoic acid (DHA) were unchanged. Furthermore EPA-E ingestion significantly decreased the Bmax of the AcLDL receptor without affecting the Kd in rat peritoneal macrophages. In addition, specific proteolytic degradation of AcLDL was also dose dependently inhibited by EPA-E feeding, indicating that the number of AcLDL receptor was significantly decreased after EPA-E ingestion. These findings indicate that EPA-E feeding inhibited CE accumulation mainly by decreasing the AcLDL receptors in macrophages. We speculate that EPA inhibits foam cell formation and this inhibitory effect may partly account for its anti-atherogenic action.