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

Vladimir R. Babaev, Liying Li, Sanket Shah, Sergio Fazio, MacRae F. Linton, James M. May

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1751-1757
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number9
StatePublished - Sep 2010
Externally publishedYes


  • antioxidants
  • atherosclerosis
  • genetically altered mice
  • nutrition

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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