GeneticsLandmark
Landmark Nature paper shows CETP-expressing transgenic mice develop far worse atherosclerosis than non-expressing controls (Nature 1993)
Original title: Severe atherosclerosis in transgenic mice expressing simian cholesteryl ester transfer protein
CETP mediates a heteroexchange of cholesterol ester for triglyceride between HDL, whose core lipid is cholesterol ester, and VLDL, whose core lipid is triglyceride, so animals expressing CETP tend toward higher VLDL and LDL cholesterol while those lacking CETP activity tend toward high HDL cholesterol. Since VLDL and LDL drive atherosclerotic progression while HDL is anti-atherogenic, the authors hypothesized CETP could itself be atherogenic, accelerating lesion progression once the other conditions for atherosclerosis are present. Transgenic mice expressing CETP were found to develop much more severe atherosclerosis than non-expressing controls, with the authors attributing the increased lesion severity largely to CETP-induced changes in the lipoprotein profile, providing the foundational in vivo demonstration of CETP's proatherogenic potential that underpins the rationale for CETP-inhibitor drug development.
Original abstract
Cholesteryl ester transfer protein (CETP) is a plasma protein that mediates the exchange of neutral lipids among the lipoprotein. Because the principal core lipid of very-low-density lipoprotein (VLDL) is triglyceride and that of high-density lipoprotein (HDL) is cholesterol ester, CETP mediates a 'heteroexchange' of cholesterol ester for triglyceride between those lipoproteins. As a result, animals that express CETP tend to have higher VLDL and low-density lipoprotein (LDL) cholesterol levels, whereas those with no CETP activity tend to have high HDL cholesterol levels. Because VLDL and LDL are associated with the progression of atherosclerosis, and HDL are considered anti-atherogenic, CETP could be an 'atherogenic' protein, that is, given the other conditions required for atherosclerosis to develop, expression of CETP would accelerate the rate at which the arterial lesions progress. We report here that transgenic mice expressing CETP had much worse atherosclerosis than did non-expressing controls, and we suggest that the increase in lesion severity was due largely to CETP-induced alterations in the lipoprotein profile.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.