Red wine polyphenolic compounds inhibit atherosclerosis in apolipoprotein E-deficient mice independently of effects on lipid peroxidation

Abstract

Background: Lipid peroxidation is thought to play an important role in the pathogenesis of atherosclerosis. Fatty acid peroxidation products such as hydroxyeicosatetraenoic acids and F2-isoprostanes have been found in advanced human atherosclerotic plaques. However, little is known about the formation of these products during lesion development. Objective: This study examined stable biomarkers of lipid oxidative damage in relation to atherosclerotic disease progression in apolipoprotein E-deficient (Apoe -/-) mice and retardation of the disease by red wine polyphenols. Design: One hundred male Apoe-/- mice and 50 male control (C57BL/6J) mice were given a high-fat, high-cholesterol diet for 20 wk. To examine the effect of the polyphenolic compounds on lesion development, 50 of the Apoe -/- mice were also given dealcoholized red wine for the duration of the study. Results: Aortic lipid deposition was significantly greater in the Apoe-/- mice than in the control mice (P < 0.01). Plasma and aortic F2-isoprostanes did not differ between the treatment groups. Plasma concentrations of monocyte chemoattractant protein 1, which has been implicated in the development of atherosclerosis, were significantly higher in the Apoe-/- mice than in the control mice up to 16 wk (P < 0.05). Hydroxyeicosatetraenoic acid concentrations increased significantly over time in all groups (P < 0.05). Red wine polyphenols had no effect on markers of lipid peroxidation or monocyte chemoattractant protein 1 concentrations, but lipid deposition in the aorta at age 26 wk was significantly less in the mice given red wine than in those not given red wine. Conclusion: These results suggest that lipid deposition is independent of lipid oxidation and that the protective action of red wine polyphenols is independent of any antioxidant action of these compounds. © 2004 American Society for Clinical Nutrition.