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  • Title: Cholesteryl ester transfer protein (CETP) expression protects against diet induced atherosclerosis in SR-BI deficient mice.
    Author: Harder C, Lau P, Meng A, Whitman SC, McPherson R.
    Journal: Arterioscler Thromb Vasc Biol; 2007 Apr; 27(4):858-64. PubMed ID: 17272756.
    Abstract:
    OBJECTIVE: To determine whether expression of the human CETP transgene protects against diet-induced atherosclerosis in SR-BI deficient mice. METHODS AND RESULTS: SR-BI deficient (-/-) mice were crossed with CETP transgenic (CETPtg) mice to produce a colony of SR-BI(-/-) x CETPtg mice in a C57Bl/6 background. Age and sex matched groups of genetically modified and wild-type C57Bl/6 mice were fed a high fat, high cholesterol diet for 22 weeks. In both wild-type and SR-BI(-/-) mice, expression of the CETP transgene reduced the cholesterol content and increased the density of lipoprotein particles in the HDL density range. In SR-BI(-/-) x CETPtg mice, CETP activity inversely correlated with total plasma cholesterol levels and shifted the buoyant HDL typical of SR-BI deficiency toward a more normal density HDL particle. Atherosclerosis at the level of the aortic arch was evident in both male and female SR-BI deficient mice but occurred to a greater extent in the females. Expression of CETP markedly attenuated the development of atherosclerosis in SR-BI deficient mice fed an atherogenic diet (P<0.003). CONCLUSIONS: Expression of the human CETP transgene protects SR-BI deficient mice from atherosclerosis, consistent with a role for CETP in remodeling HDL and providing an alternative pathway for the selective uptake of HDL-CE by the liver.
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