SEVERE ATHEROSCLEROSIS IN TRANSGENIC MICE EXPRESSING SIMIAN CHOLESTERYL ESTER TRANSFER PROTEIN

CHOLESTERYL ester transfer protein (CETP) is a plasma protein that med iates the exchange of neutral lipids among the lipoproteins1-3. Becaus e the principal core lipid of very-low-density lipoprotein (VLDL) is t riglyceride and that of high-density lipoprotein (HDL) is cholesterol ester, CETP mediates a 'heteroexchange' of cholesterol ester for trigl yceride between those lipoproteins. As a result, animals that express CETP tend to have higher VLDL and low-density lipoprotein (LDL) choles terol levels, whereas those with no CETP activity tend to have high HD L cholesterol levels2. Because VLDL and LDL are associated with the pr ogression of atherosclerosis, and HDL are considered anti-atherogenic, CETP could be an 'atherogenic' protein, that is, given the other cond itions required for atherosclerosis to develop, expression of CETP wou ld accelerate the rate at which the arterial lesions progress. We repo rt here that transgenic mice expressing CETP had much worse atheroscle rosis than did non-expressing controls, and we suggest that the increa se in lesion severity was due largely to CETP-induced alterations in t he lipoprotein profile.