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

BACKGROUND: Lipid peroxidation is thought to play an important role in the pathogenesis of atherosclerosis. Fatty acid peroxidation products such as hydroxyeicosatetraenoic acids and F(2)-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 F(2)-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.