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Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice
Author(s) -
Witting Paul K.,
Pettersson Knut,
Östlund-Lindqvist Anne-Margret,
Westerlund Christer,
Eriksson Annika Westin,
Stocker Roland
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.6.667
Subject(s) - apolipoprotein b , lipoprotein , ldl receptor , apolipoprotein e , knockout mouse , chemistry , low density lipoprotein receptor related protein 8 , medicine , lipid peroxidation , apolipoprotein c2 , receptor , endocrinology , cholesterol , very low density lipoprotein , oxidative stress , disease
Antioxidants can inhibit atherosclerosis in animals, though it is not clear whether this is due to the inhibition of aortic lipoprotein lipid (per)oxidation. Coantioxidants inhibit radical‐induced, tocopherol‐mediated peroxidation of lipids in lipoproteins through elimination of tocopheroxyl radical. Here we tested the effect of the bisphenolic probucol metabolite and coantioxidant H 212/43 on atherogenesis in apolipoprotein E and low density lipoprotein (LDL) receptor gene double knockout (apoE‐/‐;LDLr‐/‐) mice, and how this related to aortic lipid (per)oxidation measured by specific HPLC analyses. Dietary supplementation with H 212/43 resulted in circulating drug levels of ∼200 µM, increased plasma total cholesterol slightly and decreased plasma and aortic α‐tocopherol significantly relative to age‐matched control mice. Treatment with H 212/43 increased the antioxidant capacity of plasma, as indicated by prolonged inhibition of peroxyl radical‐induced, ex vivo lipid peroxidation. Aortic tissue from control apoE‐/‐;LDLr‐/‐ mice contained lipid hydro(pero)xides and substantial atherosclerotic lesions, both of which were decreased strongly by supplementation of the animals with H 212/43. The results show that a coantioxidant effectively inhibits in vivo lipid peroxidation and atherosclerosis in apoE‐/‐;LDLr‐/‐ mice, consistent with though not proving a causal relationship between aortic lipoprotein lipid oxidation and atherosclerosis in this model of the disease.—Witting, P. K., Pettersson, K., Östlund‐Lindqvist, A.‐M., Westerlund, C., Westin Eriksson, A., Stocker, R. Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice. FASEB J. 13, 667–675 (1999)