A role for reduced coenzyme Q in atherosclerosis?
Substantial evidence implicates oxidative modification of low density lipoprotein (LDL) as an important event contributing to atherogenesis. As a result, the elucidation of the molecular mechanisms by which LDL is oxidized and how such oxidation is prevented by antioxidants has been a significant research focus. Studies on the antioxidation of LDL lipids have focused primarily on alpha-tocopherol (alpha-TOH), biologically and chemically the most active form of vitamin E and quantitatively the major lipid-soluble antioxidant in extracts prepared from human LDL. In addition to alpha-TOH, plasma LDL also contains low levels of ubiquinol-10 (CoQ10H2; the reduced form of coenzyme Q10). Recent studies have shown that in oxidizing plasma lipoproteins alpha-TOH can exhibit anti- or pro-oxidant activities for the lipoprotein's lipids exposed to a vast array of oxidants. This article reviews the molecular action of alpha-TOH in LDL undergoing "mild" radical-initiated lipid peroxidation, and discusses how small levels of CoQ10H2 can represent an efficient antioxidant defence for lipoprotein lipids. We also comment on the levels alpha-TOH, CoQ10H2 and lipid oxidation products in the intima of patients with coronary artery disease and report on preliminary studies examining the effect of coenzyme Q10 supplementation on atherogenesis in apolipoprotein E knockout mice.
Thomas
S R
SR
Biochemistry Group, Heart Research Institute, Camperdown, NSW, Australia.
Witting
P K
PK
Stocker
R
R
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001161:Arteriosclerosis / Q000503:physiopathology*; D003067:Coenzymes; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D051379:Mice; D008956:Models, Chemical; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000502:physiology*; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D003067:Coenzymes; D005609:Free Radicals; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014451:Ubiquinone; D014810:Vitamin E; C024989:coenzyme Q10