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.


METHODS
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.


CONCLUSIONS
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.
Waddington
Emma
E
School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, Perth, Australia.
Puddey
Ian B
IB
Croft
Kevin D
KD
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000517:prevention & control*; D018932:Chemokine CCL2 / Q000097:blood; D002784:Cholesterol / Q000097:blood; D005419:Flavonoids / Q000627:therapeutic use*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000627:therapeutic use*; D059808:Polyphenols; D051381:Rats; D014920:Wine
D001057:Apolipoproteins E; D018932:Chemokine CCL2; D005419:Flavonoids; D006893:Hydroxyeicosatetraenoic Acids; D010636:Phenols; D059808:Polyphenols; D002784:Cholesterol