Aim: Prescription eicosapentaenoic acid (EPA) reduced cardiovascular events in the REDUCE-IT study population, including patients with diabetes. As EPA has been previously shown to reduce LDL oxidation, we investigated if it may prevent HDL oxidation at a pharmacologic dose. Atheroprotective properties of HDL are compromised in patients with diabetes due to oxidative damage and glycation.

Methods: Isolated human HDL at 200 µg/mL was incubated with vehicle or EPA at levels that match plasma concentrations (∼10 µM) at 4 g/d. All samples were subjected to oxidation over 6 hour under low and high glucose (200 mg/dL) conditions.

Results: EPA inhibited HDL oxidation in a highly dose- and time-dependent manner. At lower concentrations (≤ 3.5 µM), EPA inhibited oxidation until 4 hour or less. At higher concentrations (>7.0 µM), EPA inhibited HDL oxidation 6 hour. At 10.0 µM, EPA inhibited HDL oxidation by 80% (p<0.001) at 6 hour. Large effect shifts were observed with relatively small concentration shifts, with the critical concentration shifts being time-dependent. Similar antioxidant effects were observed with hyperglycemia.

Conclusions: These data support concentration-dependent antioxidant effects for EPA that require pharmacologic concentrations for sustained activity. These effects of EPA may provide one potential mechanism for cardiovascular benefits in patients with diabetes.

S. Sherratt: None. R. Mason: Consultant; Self; Amarin Corporation. Research Support; Self; Amarin Corporation, Amgen Inc., Novartis AG, Pfizer Inc. Speaker's Bureau; Self; Pfizer Inc.

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