Administration of high dose eicosapentaenoic acid enhances anti-inflammatory properties of high-density lipoprotein in Japanese patients with dyslipidemia

Objective: It has been reported that high-density lipoprotein (HDL) loses anti-inflammatory function and promotes atherosclerosis under pathological conditions. However, no pharmacological therapy to improve HDL function is currently available. We aimed to evaluate the effect of oral administration of eicosapentaenoic acid (EPA) on HDL function. Methods: Japanese patients with dyslipidemia were treated with EPA (1800 mg/day, 4 weeks), and anti-inflammatory functions of HDL were assessed utilizing in vitro cell-based assays. Results: The EPA treatment did not change serum cholesterol and triglyceride levels, but it significantly increased EPA concentrations in the serum and HDL fraction. The EPA/arachidonic acid ratio in the HDL was in proportion to that in the serum, suggesting that the orally administered EPA was efficiently incorporated into the HDL particles. The HDL after EPA treatment showed significantly increased activity of anti-oxidative enzyme, paraoxonase-1. 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 augmented cholesterol efflux capacity from macrophages. Conclusion: Oral administration of EPA regenerated anti-oxidative and anti-inflammatory functions of HDL, and promoted cholesterol efflux from macrophages. Therefore, EPA may transform “dysfunctional HDL” to “functional”, in patients with coronary risk factors.