Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice.

Babaev VR, Li L, Shah S, Fazio S, Linton MF, May JM
Arterioscler Thromb Vasc Biol. 2010 30 (9): 1751-7

PMID: 20558818 · PMCID: PMC2924448 · DOI:10.1161/ATVBAHA.110.209502

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.

MeSH Terms (30)

Animals Aortic Diseases Apolipoproteins E Ascorbic Acid Ascorbic Acid Deficiency Atherosclerosis Brain Dietary Supplements Disease Models, Animal Disease Progression Female L-Gulonolactone Oxidase Lipid Peroxidation Liver Macrophages Male Mice Mice, Inbred C57BL Mice, Knockout Myocardium Organic Anion Transporters, Sodium-Dependent Oxidative Stress Severity of Illness Index Sex Factors Sodium-Coupled Vitamin C Transporters Symporters Time Factors Vitamin E Vitamin E Deficiency Vitamins

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