Dietary Cosupplementation With Vitamin E and Coenzyme Q10 Inhibits Atherosclerosis in Apolipoprotein E Gene Knockout Mice

Abstract— Intimal oxidation of LDL is considered an important early event in atherogenesis, and certain antioxidants are antiatherogenic. Dietary coenrichment with vitamin E (VitE) plus ubiquinone-10 (CoQ10, which is reduced during intestinal uptake to the antioxidant ubiquinol-10, CoQ10H2) protects, whereas enrichment with VitE alone can increase oxidizability of LDL lipid against ex vivo oxidation. In the present study, we tested whether VitE plus CoQ10 cosupplementation is more antiatherogenic than either antioxidant alone, by use of apolipoprotein E-deficient (apoE−/−) mice fed a high-fat diet without (control) or with 0.2% (wt/wt) VitE, 0.5% CoQ10, or 0.2% VitE plus 0.5% CoQ10 (VitE+CoQ10) for 24 weeks. None of the supplements affected plasma cholesterol concentrations, whereas in the VitE and CoQ10 groups, plasma level of the respective supplement increased. Compared with control, plasma from CoQ10 or VitE+CoQ10 but not VitE-supplemented animals was more resistant to ex vivo lipid peroxidation induced by peroxyl radicals. VitE supplementation increased VitE levels in aorta, heart, brain, and skeletal muscle, whereas CoQ10 supplementation increased CoQ10 only in plasma and aorta and lowered tissue VitE. All treatments significantly lowered aortic cholesterol compared with control, but only VitE+CoQ10 supplementation significantly decreased tissue lipid hydroperoxides when expressed per parent lipid. In contrast, none of the treatments affected aortic ratios of 7-ketocholesterol to cholesterol. Compared with controls, VitE+CoQ10 supplementation decreased atherosclerosis at the aortic root and arch and descending thoracic aorta to an extent that increased with increasing distance from the aortic root. CoQ10 significantly inhibited atherosclerosis at aortic root and arch, whereas VitE decreased disease at aortic root only. Thus, in apoE−/− mice, VitE+CoQ10 supplements are more antiatherogenic than CoQ10 or VitE supplements alone and disease inhibition is associated with a decrease in aortic lipid hydroperoxides but not 7-ketocholesterol.