© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Dietary ß-Carotene and 
-Tocopherol Combination Does Not Inhibit Atherogenesis in an ApoE–Deficient Mouse Model
From the Institute of Lipid and Atherosclerosis Research (A.S., P.K., H.L., D.H.) and Research Unit of Autoimmune Diseases (J.G., B.G.), Department of Medicine `B', Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Correspondence to Dror Harats, MD, Institute of Lipid and Atherosclerosis Research, Sheba Medical Center, Tel-Hashomer, 52621, Israel. E-mail dharats{at}post.tau.ac.il
Abstract—Although lipid
oxidation plays a major role in atherogenesis, the role of antioxidants
in the prevention and treatment of the process is not clear.
Apolipoprotein (apo) E–deficient mice develop spontaneous
atherosclerotic lesions in major arteries. The presence of oxidized
lipoprotein epitopes in the lesion suggests that oxidation reactions
are involved in atherogenesis in this mouse model, but the
inhibitory effect of antioxidants on atherogenesis in the
model is controversial. To test the effect of dietary antioxidants on
atherogenesis, male apoE-deficient mice (n=15) were fed a standard chow
diet supplemented with 0.05% 
-tocopherol and 0.05%
all-trans ß-carotene. A control group (n=15) received no antioxidant
supplement. At the end of the trial, mice consuming vitamins had 5x
more plasma vitamin E but undetectable ß-carotene levels. However,
liver levels of the ß-carotene metabolite, retinyl palmitate, were
higher in antioxidant-treated mice compared with control mice. The
antioxidants had no effect on lipoprotein or on plasma
anti–oxidatively modified low density lipoproteins (anti-oxLDL)
antibody levels. The vitamins had a small but insignificant effect on
lipoprotein resistance to ex vivo oxidation, determined by a longer lag
period of conjugated diene formation. Atherosclerosis,
determined by the lesion size at the aortic sinus, was insignificantly
suppressed in antioxidant-treated mice (mean area±SE, 20 000±7129
versus 13 281±5861 µm2; P=0.40).
The aortic atherosclerotic lesion area was similar in both experimental
groups (2.55±0.65% and 2.08±0.5% of total aortic area in the
control and antioxidant group, respectively; P=0.58).
The results of the current study suggest that moderate levels of
synthetic antioxidant vitamins have no effect on atherogenesis in
apoE-deficient mice.
Key Words: atherosclerosis • oxidation • antioxidants • ß-carotene • -tocopherol • antibodies • mouse • apoE
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