LDL and apoB
CETP drives atherosclerosis mainly by raising VLDL-cholesterol, not by lowering HDL-cholesterol, in APOE*3-Leiden mice (Atherosclerosis 2009)
Original title: Human CETP aggravates atherosclerosis by increasing VLDL-cholesterol rather than by decreasing HDL-cholesterol in APOE*3-Leiden mice
Comparing APOE*3-Leiden (E3L) mice with and without human CETP expression, a low-cholesterol diet produced a 4-fold higher VLDL-cholesterol level and a 9-fold larger atherosclerotic lesion area in E3L.CETP mice versus E3L mice. When E3L mice were instead fed a high-cholesterol diet to match the VLDL-cholesterol levels seen in E3L.CETP mice, they developed a similar lesion area, showing that CETP's proatherogenic effect is largely explained by its VLDL-cholesterol-raising action. Despite similar atherosclerosis, E3L.CETP mice still had 49% lower HDL-cholesterol than the high-cholesterol E3L mice, indicating CETP's HDL-lowering effect contributed little to lesion development in this setting; lesions in CETP-expressing mice were also enriched in collagen.
Original abstract
Objective: Cholesteryl ester transfer protein (CETP) adversely affects the plasma lipoprotein profile by increasing VLDL-cholesterol and decreasing HDL-cholesterol. The relative contribution of either of these changes to atherosclerosis development is not known. We investigated to what extent the increase in VLDL-cholesterol can explain the atherogenic action of human CETP expression in APOE*3-Leiden (E3L) mice, a model for human-like lipoprotein metabolism.
Methods And Results: E3L mice and E3L.CETP mice were fed a low cholesterol (LC) diet, resulting in a 4-fold increased VLDL-cholesterol level as well as a 9-fold increased atherosclerotic lesion area in the aortic root in E3L.CETP mice compared to E3L-LC mice. E3L mice fed a high cholesterol (HC) diet to match the increased VLDL-cholesterol levels in E3L.CETP mice, displayed a similar atherosclerotic lesion area as observed in E3L.CETP mice. Hence, the CETP-induced raise in atherosclerosis can largely be explained by increased VLDL-cholesterol. Despite similar atherosclerosis development, E3L.CETP mice had lower HDL-cholesterol as compared to E3L-HC mice (-49%) indicating that the HDL-cholesterol lowering effect of CETP is unlikely to contribute to atherosclerosis development in this experimental setting. Remarkably, atherosclerotic lesions in CETP-expressing mice were enriched in collagen, suggesting a role of CETP or the diet in modifying lesion collagen content.
Conclusions: In this experimental setting, the proatherogenic effect of CETP is largely explained by increased VLDL-cholesterol.
HDL biologyLDL and apoBmechanisms
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.