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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: 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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Does combined vitamin C and vitamin E deficiency worsen early atherosclerosis in apolipoprotein E-deficient mice? Context: 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). 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.
assistant
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. Final Decision: yes