Anti-atherogenic effect of coenzyme Q10 in apolipoprotein E gene knockout mice

Oxidation of low-density lipoprotein (LDL) lipid is implicated in atherogenesis and certain antioxidants inhibit atherosclerosis. Ubiquinol-10 (CoQ(10)H(2)) inhibits LDL lipid peroxidation in vitro although it is not known whether such activity occurs in vivo, and, if so, whether this is anti-atherogenic. We therefore tested the effect of ubiquinone-10 (CoQ(10)) supplemented at 1% (w/w) on aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet. Hydroperoxides of cholesteryl esters and triacylglycerols (together referred to as LOOM) and their corresponding alcohols were used as the marker for lipoprotein lipid oxidation. Atherosclerosis was assessed by morphometry at the aortic root, proximal and distal arch, and the descending thoracic and abdominal aorta. Compared to controls, CoQ(10)-treatment increased plasma coenzyme Q, ascorbate, and the CoQ(10)H(2): CoQ(10) + CoQ(10)H(2) ratio, decreased plasma alpha-tocopherol (alpha-TOH), and had no effect on cholesterol and cholesterylester alcohols (CE-OH). Plasma from CoQ(10)-supplemented mice was more resistant to ex vivo lipid peroxidation. CoQ(10) treatment increased aortic coenzyme Q and alpha-TOH and decreased the absolute concentration of LOOM, whereas tissue cholesterol, cholesteryl esters, CE-OH, and LOOM expressed per bisallylic hydrogen-containing lipids were not significantly different. CoQ(10)-treatment significantly decreased lesion size in the aortic root and the ascending and the descending aorta. Together these data show that CoQ(10) decreases the absolute concentration of aortic LOOM and atherosclerosis in apoE-/- mice. (C) 2000 Elsevier Science Inc.