Anti-atherogenic effect of coenzyme Q(10) in apolipoprotein E gene knockout mice

Oxidation of low-density lipoprotein (LDL) lipid is implicated in atherogen esis and certain antioxidants inhibit atherosclerosis. Ubiquinol-10 (CoQ(10 )H(2)) inhibits LDL lipid peroxidation in vitro although it is not known wh ether such activity occurs in vivo, and, if so, whether this is anti-athero genic. We therefore tested the effect of ubiquinone-10 (CoQ(10)) supplement ed at 1% (w/w) on aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet. Hydroper oxides of cholesteryl esters and triacylglycerols (together referred to as LOOM) and their corresponding alcohols were used as the marker for lipoprot ein lipid oxidation. Atherosclerosis was assessed by morphometry at the aor tic root, proximal and distal arch, and the descending thoracic and abdomin al 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 c holesterylester 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 expr essed per bisallylic hydrogen-containing lipids were not significantly diff erent. CoQ(10)-treatment significantly decreased lesion size in the aortic root and the ascending and the descending aorta. Together these data show t hat CoQ(10) decreases the absolute concentration of aortic LOOM and atheros clerosis in apoE-/- mice. (C) 2000 Elsevier Science Inc.