Wine Flavonoids Protect against LDL Oxidation and Atherosclerosis

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Abstract:We have previously shown that consumption of red wine, but not of white wine, by healthy volunteers, resulted in the enrichment of their plasma LDL with flavonoid antioxidants such as quercetin, the potent free radicals scavenger flavanol, which binds to the LDL via a glycosidic ether bond. This phenomenon was associated with a significant three‐fold reduction in copper ion‐induced LDL oxidation. The ineffectiveness of flavonoid‐poor white wine could be overcome by grape's skin contact for 18 hours in the presence of alcohol, which extracts grape's skin flavonoids. Recently, we observed that the high antioxidant potency of Israeli red wine could be related to an increased content of flavonols, which are very potent antioxidants and their biosynthesis is stimulated by sunlight exposure. To find out the effect (and mechanisms) of red wine consumption on atherosclerosis, we used the apo E deficient (E0) mice. In these mice, red wine consumption for two months resulted in a 40% decrement in basal LDL oxidation, a similar decrement in LDL oxidizability and aggregation, a 35% reduction in lesion size, and a marked attenuation in the number and morphology of lesion's macrophage foam cells. Red wine consumption resulted in accumulation of flavonoids in the mouse macrophages and these cells oxidized LDL and took up LDL about 40% less than macrophages from placebo‐treated mice. Finally, the activity of serum paraoxonase (which can hydrolyze specific lipid peroxides in oxidized LDL and in atherosclerotic lesions) was significantly increased following consumption of red wine by E0mice. Red wine consumption thus acts against the accumulation of oxidized LDL in lesions as a first line of defense (by a direct inhibition of LDL oxidation), and as a second line of defense (by paraoxonase elevation and removal of atherogenic lesion's and lipoprotein's oxidized lipids).