TY - JOUR
T1 - Combined vitamin C and vitamin e deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice
AU - Babaev, Vladimir R.
AU - Li, Liying
AU - Shah, Sanket
AU - Fazio, Sergio
AU - Linton, MacRae F.
AU - May, James M.
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - antioxidants
KW - atherosclerosis
KW - genetically altered mice
KW - nutrition
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U2 - 10.1161/ATVBAHA.110.209502
DO - 10.1161/ATVBAHA.110.209502
M3 - Article
C2 - 20558818
AN - SCOPUS:77955985049
SN - 1079-5642
VL - 30
SP - 1751
EP - 1757
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 9
ER -