First Author | Babaev VR | Year | 2010 |
Journal | Arterioscler Thromb Vasc Biol | Volume | 30 |
Issue | 9 | Pages | 1751-7 |
PubMed ID | 20558818 | Mgi Jnum | J:179551 |
Mgi Id | MGI:5302633 | Doi | 10.1161/ATVBAHA.110.209502 |
Citation | Babaev VR, et al. (2010) Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 30(9):1751-7 |
abstractText | OBJECTIVE: To assess the role of combined deficiencies of vitamins C and E on the earliest stages of atherosclerosis (an inflammatory condition associated with oxidative stress), 4 combinations of vitamin supplementation (low C/low E, low C/high E, high C/low E, and high C/high E) were studied in atherosclerosis-prone apolipoprotein E-deficient mice also unable to synthesize their own vitamin C (gulonolactone oxidase(-/-)); and to evaluate the effect of a more severe depletion of vitamin C alone in a second experiment using gulonolactone oxidase(-/-) mice carrying the hemizygous deletion of SVCT2 (the vitamin C transporter). METHODS AND RESULTS: After 8 weeks of a high-fat diet (16% lard and 0.2% cholesterol), atherosclerosis developed in the aortic sinus areas of mice in all diet groups. Each vitamin-deficient diet significantly decreased liver and brain contents of the corresponding vitamin. Combined deficiency of both vitamins increased lipid peroxidation, doubled plaque size, and increased plaque macrophage content by 2- to 3-fold in male mice, although only plaque macrophage content was increased in female mice. A more severe deficiency of vitamin C in gulonolactone oxidase(-/-) mice with defective cellular uptake of vitamin C increased both oxidative stress and atherosclerosis in apolipoprotein E(-/-) mice compared with littermates receiving a diet replete in vitamin C, again most clearly in males. CONCLUSIONS: Combined deficiencies of vitamins E and C are required to worsen early atherosclerosis in an apolipoprotein E-deficient mouse model. However, a more severe cellular deficiency of vitamin C alone promotes atherosclerosis when vitamin E is replete. |