Coenzyme Q(10) supplementation inhibits aortic lipid oxidation but fails to attenuate intimal thickening in balloon-injured New Zealand white rabbits.
Oxidized lipoproteins are implicated in atherosclerosis, and some antioxidants attenuate the disease in animals. Coenzyme Q(10) (CoQ(10)) in its reduced form, ubiquinol-10, effectively inhibits lipoprotein oxidation in vitro and in vivo; CoQ(10) supplements also inhibit atherosclerosis in apolipoprotein E gene knockout (apoE-/-) mice. Here we tested the effect of dietary CoQ(10) supplements on intimal proliferation and lipoprotein lipid oxidation in balloon-injured, hypercholesterolemic rabbits. Compared to nonsupplemented chow, CoQ(10) supplementation (0.5% and 1.0%, w/w) significantly increased the plasma concentration of CoQ(10) and the resistance of plasma lipids to ex vivo oxidation. CoQ(10) supplements also increased the content of CoQ(10) in the aorta and liver, but not in the brain, skeletal muscle, kidney, and heart. Surprisingly, CoQ(10) supplementation at 1% increased the aortic concentrations of all lipids, particularly triacylglycerols, although it significantly inhibited the proportion of triacylglycerols present as hydroperoxides by > 80%. The observed increase in vessel wall lipid content was reflected in elevated plasma concentrations of cholesterol, cholesteryl esters and triacylglycerols, and hepatic levels of mRNA for 3-hydroxy-3-methylglutaryl-coenzyme A reductase. CoQ(10) supplements did not attenuate lesion formation, assessed by the intima-to-media ratio of injured aortic vessels. Thus, like in apoE-/- mice, a high dose of supplemented CoQ(10) inhibits lipid oxidation in the artery wall of balloon-injured, hypercholesterolemic rabbits. However, unlike its antiatherosclerosis activity in the mice, CoQ(10) does not inhibit intimal hyperplasia in rabbits, thereby dissociating this disease process from lipid oxidation in the vessel wall.
Choy
Katherine J
KJ
Biochemistry Group, The Heart Research Institute, Camperdown, New South Wales, Australia.
Deng
Yi-Mo
YM
Hou
Jing Yun
JY
Wu
Ben
B
Lau
Antony
A
Witting
Paul K
PK
Stocker
Roland
R
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001011:Aorta / Q000473:pathology*; D002784:Cholesterol / Q000378:metabolism; D002850:Chromatography, Gel; D003067:Coenzymes; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000975:Antioxidants; D003067:Coenzymes; D005609:Free Radicals; D012333:RNA, Messenger; D014451:Ubiquinone; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; C024989:coenzyme Q10; D010100:Oxygen