Dietary Cosupplementation With Vitamin E and Coenzyme Q ₁₀ Inhibits Atherosclerosis in Apolipoprotein E Gene Knockout Mice

Abstract

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 (CoQ 10 , which is reduced during intestinal uptake to the antioxidant ubiquinol-10, CoQ 10 H 2 ) 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 CoQ 10 cosupplementation is more antiatherogenic than either antioxidant alone, by use of apolipoprotein E-deficient (apoEϪ/Ϫ) mice fed a high-fat diet without (control) or with 0.2% (wt/wt) VitE, 0.5% CoQ 10 , or 0.2% VitE plus 0.5% CoQ 10 (VitEϩCoQ 10 ) for 24 weeks. None of the supplements affected 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 VitEϩCoQ 10 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 CoQ 10 supplementation increased CoQ 10 only in plasma and aorta and lowered tissue VitE. All treatments significantly lowered aortic cholesterol compared with control, but only VitEϩCoQ 10 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, VitEϩCoQ 10 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. CoQ 10 significantly inhibited atherosclerosis at aortic root and arch, whereas VitE decreased disease at aortic root only. Thus, in apoEϪ/Ϫ mice, VitEϩCoQ 10 supplements are more antiatherogenic than CoQ 10 or VitE supplements alone and disease inhibition is associated with a decrease in aortic lipid hydroperoxides but not 7-ketocholesterol.

Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia

“…5). Both compounds are orally administered, display an excellent safety profile, even at high doses, and are given in combination to increase antioxidant capacity (20,31). We found that treated Mut −/− ;Tg INS-Alb-Mut mice experienced a significant amelioration in the loss of GFR and a normalization of plasma Lcn2 levels compared with untreated animals fed a HP diet, despite exhibiting the same magnitude of elevation of serum metabolites.…”

Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice

“…There is induction of catalase and eNOS in the aorta by vigorous exercise in hypercholesterolemic mice, and vitamin E supplementation in the exercised group does not appear to affect atherosclerosis (32). In contrast, several studies showed clear beneficial effects of vitamin E on lesion progression in hypercholesterolemic mice (37)(38)(39)(40). Consistently, there is increased atherosclerosis in hypercholesterolemic mice deficient in ␣-tocopherol transfer protein and vitamin E (41).…”

Is the Oxidative Modification Hypothesis Relevant to Human Atherosclerosis?

“…Vitamin E is the antioxidant used in most of the clinical trials to date. In mouse models of atherosclerosis it has been effective alone 32 or in combination with other antioxidants, 33,34 but most of the studies in rabbits have been negative. 35 Moreover, when administered to humans, vitamin E has been shown to have only a modest inhibitory effect on LDL oxidation ex vivo (delaying copper-induced oxidation by 15 to 20 minutes) but nowhere near the almost complete protection afforded by such a potent antioxidant as probucol (which can delay oxidation for as much as 20 hours).…”