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From the Department of Biochemistry, Faculty of Pharmaceutical Science (I.I., Y.I., S.H.), and the Second Department of Internal Medicine, School of Medicine (N.M.), Chiba University, and the Department of Laboratory Medicine, Yamagata University (Y.S.), Japan.
Correspondence to Itsuko Ishii, Department of Biochemistry, Faculty of Pharmaceutical Sciences, Chiba University, Inage-ku 1-33, Yayoi-cho, Chiba, 263, Japan.
Abstract Cholesterol metabolism in macrophages from atherosclerosis-prone C57BL/6J mice was compared with that in macrophages from atherosclerosis-resistant C3H/HeN mice. Plasma total cholesterol levels of both types of mice were significantly increased, but HDL cholesterol level was increased only in C3H/HeN mice when a high-cholesterol diet (1% cholesterol) was fed for 5 weeks. After incubation of macrophages from male and female mice on the high-cholesterol diet with ß-VLDL for 24 hours, cholesterol content in macrophages from C57BL/6J was approximately 1.5- to 2.0-fold higher than in those from C3H/HeN mice. [3H]Cholesterol oleateß-VLDL incorporation into macrophages from C57BL/6J mice on the high-cholesterol diet was greater than incorporation into those from C3H/HeN mice. The release of [3H]cholesterol from macrophages from C57BL/6J mice on the high-cholesterol diet was one seventh that from macrophages from C57BL/6J mice on the basal diet or that from macrophages from C3H/HeN mice on the basal or high-cholesterol diet. Acid cholesterol esterase activity was almost the same in macrophages from any group. Acyl CoA:cholesterol acyltransferase activity in macrophages from C57BL/6J mice on the high-cholesterol diet increased compared with that from macrophages from C57BL/6J mice on the normal diet. Neutral cholesterol esterase activity in macrophages from C57BL/6J mice was about half of that in macrophages from C3H/HeN mice independent of the type of diet. There were no sex differences in these metabolisms. Considered with our previous data, these results suggested that a high-cholesterol diet may cause metabolic changes to accumulate cholesterol ester in macrophages from C57BL/6J mice in accordance with genetic abnormalities.
Key Words: high-cholesterol diet neutral cholesterol esterase C57BL/6J mouse macrophage acyl CoA:cholesterol acyltransferase
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