Dietary cosupplementation with vitamin E and coenzyme Q(10) inhibits atherosclerosis in apolipoprotein E gene knockout mice

Intimal oxidation of LDL is considered an important early event in atheroge nesis, and certain antioxidants are antiatherogenic. Dietary coenrichment w ith vitamin E (VitE) plus ubiquinone-10 (CoQ(10), which is reduced during i ntestinal uptake to the antioxidant ubiquinol-10, CoQ(10)H(2)) protects, wh ereas enrichment with VitE alone can increase oxidizability of LDL lipid ag ainst ex vivo oxidation. In the present study, we tested whether VitE plus CoQ(10) cosupplementation is more antiatherogenic than either antioxidant a lone, by use of apolipoprotein E-deficient (apoE(-/-)) mice fed a high-fat diet without (control) or with 0.2% (wt/wt) VitE, 0.5% CoQ(10), or 0.2% Vit E plus 0.5% CoQ(10) (VitE+CoQ(10),) for 24 weeks. None of the supplements a ffected plasma cholesterol concentrations, whereas in the VitE and CoQ(10) groups, plasma level of the respective supplement increased, Compared with control, plasma from CoQ(10) or VitE+CoQ(10) but not VitE-supplemented anim als was more resistant to ex vivo lipid peroxidation induced by peroxyl rad icals. VitE supplementation increased VitE levels in aorta, heart, brain, a nd skeletal muscle, whereas CoQ(10) supplementation increased CoQ(10) only in plasma and aorta and lowered tissue VitE. All treatments significantly l owered aortic cholesterol compared with control, but only VitE+CoQ(10) supp lementation significantly decreased tissue lipid hydroperoxides when expres sed per parent lipid. In contrast, none of the treatments affected aortic r atios of 7-ketocholesterol to cholesterol. Compared with controls, VitE+CoQ (10) supplementation decreased atherosclerosis at the aortic root and arch and descending thoracic aorta to an extent that increased with increasing d istance from the aortic root. CoQ(10) significantly inhibited atheroscleros is at aortic root and arch, whereas VitE decreased disease at aortic root o nly. Thus, in apoE(-/-) mice, VitE+CoQ(10) supplements are more antiatherog enic than CoQ(10) or VitE supplements alone and disease inhibition is assoc iated with a decrease in aortic lipid hydroperoxides but not 7-ketocholeste rol.