HDL biology
CETP expression protects SR-BI-deficient mice from diet-induced atherosclerosis by remodeling buoyant HDL toward normal density (Arterioscler Thromb Vasc Biol 2007)
Original title: Cholesteryl ester transfer protein (CETP) expression protects against diet induced atherosclerosis in SR-BI deficient mice
SR-BI-deficient mice were crossed with CETP transgenic mice to produce SR-BI(-/-) x CETPtg mice, and age- and sex-matched 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-deficient backgrounds, CETP transgene expression reduced HDL cholesterol content and increased HDL particle density; in SR-BI(-/-) x CETPtg mice, CETP activity correlated inversely with total plasma cholesterol and shifted the buoyant HDL typical of SR-BI deficiency toward more normal density. Aortic arch atherosclerosis occurred in both sexes of SR-BI-deficient mice, more extensively in females, but CETP expression markedly attenuated atherosclerosis development in SR-BI-deficient mice fed the atherogenic diet (P < 0.003), consistent with a role for CETP in remodeling HDL and providing an alternative hepatic uptake pathway for HDL cholesteryl ester.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.