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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1412.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Cholesteryl Ester Transfer Protein Expression Prevents Diet-Induced Atherosclerotic Lesions in Male db/db Mice

Paul S. MacLean; Joseph F. Bower; Satyaprasad Vadlamudi; Jody N. Osborne; John F. Bradfield; Hubert W. Burden; William H. Bensch; Raymond F. Kauffman; Hisham A. Barakat

From the Departments of Biochemistry (P.S.M., J.F.B., S.V., H.A.B.), Comparative Medicine (J.N.O., J.F.B.), and Anatomy and Cell Biology (H.W.B.), Brody School of Medicine, East Carolina University, Greenville, NC, and Lilly Research Laboratories (W.H.B., R.F.K.), a Division of Eli Lilly and Company, Indianapolis, Ind.

Correspondence to Paul S. MacLean, PhD, University of Colorado Health Sciences Center, Center for Human Nutrition, 4200 E 9th Ave, C225, Denver, CO 80262. E-mail Paul.MacLean{at}UCHSC.edu

Objective— Accompanying more atherogenic lipoprotein profiles and an increased incidence of atherosclerosis, plasma cholesteryl ester transfer protein (CETP) is depressed in diabetic obese patients compared with nondiabetic obese counterparts. The depressed levels of CETP in the plasma of diabetic obese individuals may contribute to the development of an atherogenic lipoprotein profile and atherogenesis. We have examined the effect of CETP expression on vascular health in the db/db model of diabetic obesity.

Methods and Results— Transgenic mice expressing the human CETP minigene were crossed with db/db strain, and 3 groups of offspring (CETP, db, and db/CETP) were placed on an atherogenic diet for 16 weeks. The proximal aorta was then excised and examined for the presence of atherosclerotic plaques. In db mice, 9 of 11 had intimal lesions with a mean area of 26 098±7486 µm². No lesions greater than 1000 µm² were observed in db/CETP or CETP mice. CETP-expressing mice had lower circulating cholesterol concentrations than db mice. Fractionating plasma lipids by FPLC indicated that the difference in total cholesterol was primarily attributable to differences in VLDL and LDL.

Conclusions— The expression of human CETP in db/db mice prevented the formation of diet-induced lesions, suggesting an antiatherogenic effect of CETP in the context of diabetic obesity.

Key Words: cholesterol • FPLC • VLDL • LDL • HDL obesity

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