Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volume 68, Issue 1, Pages 33-40Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0000000000000379
Keywords
omega-3 fatty acid; eicosapentaenoic acid; small; dense LDL; docosahexaenoic acid; atorvastatin; triglycerides
Funding
- Amarin Pharma Inc, Bedminster, NJ
- Amarin Pharma Inc.
- Pfizer
- Novartis
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Eicosapentaenoic acid (EPA) is a triglyceride-lowering agent that reduces circulating levels of the apolipoprotein B (apoB)-containing lipoprotein particles small dense low-density lipoprotein (sdLDL), very-low-density lipoprotein (VLDL), and oxidized low-density lipoprotein (LDL). These benefits may result from the direct antioxidant effects of EPA. To investigate this potential mechanism, these particles were isolated from human plasma, preincubated with EPA in the absence or presence of atorvastatin (active) metabolite, and subjected to copper-initiated oxidation. Lipid oxidation was measured as a function of thiobarbituric acid reactive substances formation. EPA inhibited sdLDL (IC50 similar to 2.0 mu M) and LDL oxidation (IC50 similar to 2.5 mu M) in a dose-dependent manner. Greater antioxidant potency was observed for EPA in VLDL. EPA inhibition was enhanced when combined with atorvastatin metabolite at low equimolar concentrations. Other triglyceride-lowering agents (fenofibrate, niacin, and gemfibrozil) and vitamin E did not significantly affect sdLDL, LDL, or VLDL oxidation compared with vehicle-treated controls. Docosahexaenoic acid was also found to inhibit oxidation in these particles but over a shorter time period than EPA. These data support recent clinical findings and suggest that EPA has direct antioxidant benefits in various apoB-containing subfractions that are more pronounced than those of other triglyceride-lowering agents and docosahexaenoic acid.
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