HDL biologyLandmark
CETP expression multiplies atherosclerotic lesion area 7-fold in the new E3L.CETP mouse model (Arterioscler Thromb Vasc Biol 2006)
Original title: Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice
Crossbreeding APOE*3-Leiden (E3L) mice with human CETP transgenic mice, CETP expression raised total cholesterol 43% on chow (P<0.05) and shifted cholesterol distribution from HDL toward VLDL/LDL on both chow and a Western-type 0.25% cholesterol diet, which raised total cholesterol 4.3-fold in both strains (P<0.01). Plasma from CETP.E3L mice had 39% reduced capacity to induce SR-BI-mediated cholesterol efflux versus E3L plasma (P<0.05). After 19 weeks on the Western-type diet, CETP.E3L mice developed 7.0-fold more atherosclerotic lesion area in the aortic root than E3L mice (P<0.0001). The authors conclude CETP is a clear pro-atherogenic factor in this model and propose the new CETP.E3L mouse as a valuable tool for preclinical testing of HDL-raising interventions.
Original abstract
Objective: The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile.
Methods And Results: E3L mice were crossbred with human CETP transgenic mice. On a chow diet, CETP expression increased plasma total cholesterol (TC) (+43%; P<0.05). To evaluate the effects of CETP on the development of atherosclerosis, mice were fed a Western-type diet containing 0.25% cholesterol, leading to 4.3-fold elevated TC levels in both E3L and CETP.E3L mice (P<0.01). On both diets, CETP expression shifted the distribution of cholesterol from high-density lipoprotein (HDL) toward very-low-density lipoprotein (VLDL)/low-density lipoprotein (LDL). Moreover, plasma of CETP.E3L mice had reduced capacity (-39%; P<0.05) to induce SR-BI-mediated cholesterol efflux from Fu5AH cells than plasma of E3L mice. After 19 weeks on the Western-type diet, CETP.E3L mice showed a 7.0-fold increased atherosclerotic lesion area in the aortic root compared with E3L mice (P<0.0001).
Conclusions: CETP expression in E3L mice shifts the distribution of cholesterol from HDL to VLDL/LDL, reduces plasma-mediated SR-BI-dependent cholesterol efflux, and represents a clear pro-atherogenic factor in E3L mice. We anticipate that the CETP.E3L mouse will be a valuable model for the preclinical evaluation of HDL-raising interventions on atherosclerosis development.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.