Abstract 14785: Oral Administration of Eicosapentaenoic Acid Ameliorates Anti-inflammatory Functions of High-Density Lipoprotein in Dyslipidemic Patients

Abstract

Objective: Previous studies have reported that inflammation converts high-density lipoprotein (HDL) to dysfunctional form lacking its anti-inflammatory properties. However, little is known about pharmacological therapy to improve HDL function. It has been recently postulated that fatty acid component in HDL-phospholipids modulates HDL functions. We investigated the effect of oral administration of high dose eicosapentaenoic acid (EPA) on HDL functions. Methods: Patients with dyslipidemia were treated with 1800 mg/day EPA for 4 weeks, and HDL fractions were isolated by ultracentrifuge before and after the EPA treatment. HDL functions were evaluated by multiple in vitro cell-based assays. Results: The EPA treatment did not affect the quantity in the serum lipid profile including serum cholesterol, triglyceride and apolipoprotein levels, but significantly increased EPA concentrations both in the serum and HDL fraction. The EPA/arachidonic acid ratio in the HDL was in proportion to that in the serum, suggesting that EPA was incorporated in HDL particles. The HDL after EPA treatment possessed high activity of paraoxonase-1, an HDL-associated anti-oxidative enzyme, compared to HDL before EPA treatment. In addition, the EPA-rich HDL significantly improved endothelial cell migration, and markedly inhibited cytokine-induced expression of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells, compared to HDL before the EPA treatment. Moreover, the EPA-rich HDL had high capacity of cholesterol efflux capacity from macrophages. Conclusion: Administration of high dose EPA improves anti-inflammatory, anti-oxidative, and cholesterol efflux capacity of HDL in dyslipidemic patients. Thus, EPA may transform “dysfunctional HDL” to “functional”, in patients with coronary risk factors.