Severe atherosclerosis in transgenic mice expressing simian cholesteryl ester transfer protein

Abstract

CHOLESTERYL ester transfer protein (CETP) is a plasma protein that mediates the exchange of neutral lipids among the lipoproteins^1–3. 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 levels². 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.