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2
Departments of
*
Medicine,
**
Pathology and
Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
2To whom correspondence should be addressed.
We evaluated the effects of vitamin E and ß-carotene on
apolipoprotein (apo)E +/- female mice, which develop atherosclerosis
only when fed diets high in triglyceride and cholesterol. Mice were fed
a nonpurified control diet (5.3 g/100 g triglyceride, 0.2 g/100 g
cholesterol), an atherogenic diet alone (15.8 g/100 g triglyceride,
1.25 g/100 g cholesterol, 0.5 g/100 g Na cholate) or the atherogenic
diet supplemented with either 0.5 g/100 g (+)-
-tocopherol
(mixed isomers); 0.5 g/100 g palm tocopherols (palm-E; 33%
-tocopherol, 16.1%
-tocotrienol, 2.3% ß-tocotrienol, 32.2%
-tocotrienol, 16.1%
-tocotrienol); 1.5 g/100 g palm-E; or 0.01
g/100 g palm-carotenoids (58% ß-carotene, 33%
-carotene, 9%
other carotenoids). Compared with mice fed the control diet, plasma
cholesterol was fourfold greater in mice fed the atherogenic diet. Mice
fed the 1.5 g/100 g palm-E supplement had 60% lower plasma
cholesterol than groups fed the other atherogenic diets. Mice fed the
atherogenic diet had markedly higher VLDL, intermediate density
lipoprotein (IDL) and LDL cholesterol and markedly lower HDL
cholesterol than the controls. Lipoprotein patterns in mice
supplemented with
-tocopherol or palm carotenoids were similar to
those of the mice fed the atherogenic diet alone, but the pattern in
mice supplemented with 1.5 g/100 g palm-E was similar to that of
mice fed the control diet. In mice fed the atherogenic diet, the
hepatic cholesterol plus cholesterol ester concentration was 4.4-fold
greater than in mice fed the control diet. Supplementing with 1.5 g/100
g palm-E lowered hepatic cholesterol plus cholesterol ester
concentration 66% compared with the atherogenic diet alone. Mice fed
the atherogenic diet had large atherosclerotic lesions at the level of
the aortic valve. With supplements of 0.5 g/100 g palm-E or 1.5
g/100 g palm-E, the size of the lesions was 92 or 98% smaller,
respectively. The 0.5 g/100 g
-tocopherol and palm carotenoid
supplements had no effect. Supplements did not alter mRNA abundance for
apolipoproteins A1, E, and C3. The beneficial effect of tocotrienols on
atherogenesis, the plasma lipoprotein profile and accumulation of
hepatic cholesterol esters cannot be attributed to their antioxidant
properties.
KEY WORDS: antioxidants ß-carotene vitamin E atherosclerosis apoE gene knockout mice
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