HDL biology
High plasma CETP does not speed reverse cholesterol transport in vivo despite raising liver cholesteryl ester uptake (Atherosclerosis 2002)
Original title: Reverse cholesterol transport in mice expressing simian cholesteryl ester transfer protein
To directly test whether CETP mobilizes cholesterol in vivo, researchers compared clearance of cationized LDL cholesterol injected into leg muscle between CETP transgenic and control mice. Retained exogenous cholesterol mass in muscle was similar between groups at day 4 (65% CETP-Tg vs. 70% controls), day 8 (52-54%), and day 28 (negligible in both). Using a nonhydrolyzable cholesteryl ester analog, clearance of the hydrolyzable label had a half-life of 4 days between day 4 and 8, while the nonhydrolyzable analog showed little loss between day 4 and 51. Liver radioactivity was higher in CETP transgenics than controls at both day 4 (3.4% vs. 1.7%) and day 8 (4.6% vs. 2.8%), with the nonhydrolyzable analog accounting for 60% of hepatic label in CETP transgenics. High plasma CETP thus increases hepatic delivery of cholesteryl ester without accelerating overall reverse cholesterol transport in vivo.
Original abstract
The role of cholesteryl ester transfer protein (CETP) in atherogenesis remains ambiguous, as both pro and antiatherogenic effects have been described. Expression of CETP increases HDL-cholesteryl ester turnover, but there is no direct evidence whether CETP mobilizes cholesterol in vivo. The rate of cholesterol removal injected into a leg muscle as cationized low density lipoprotein (cat-LDL) was compared in CETP transgenic and control mice. Four days after injection the exogenous cholesterol mass retained in muscle was 65% in CETP transgenic and 70% of injected dose in controls; it decreased to 52-54% by day 8 and negligible amounts remained on day 28. The cat-LDL was labeled with either 3H-cholesterol oleate (3H-CE) or 3H-cholesteryl oleoyl ether (3H-COE), a nonhydrolyzable analog of 3H-CE. After injection of 3H-CE cat-LDL, clearance of 3H-cholesterol had a t(1/2) of 4 days between day 4 and 8 but there was little loss of 3H-COE between day 4 and 51. Liver radioactivity on day 4 was 1.7% in controls and 3.4% in CETP transgenics; it was 2.8 and 4.6%, respectively, on day 8. 3H-COE in liver accounted for 60% of label in CETP transgenics. In conclusion, high levels of plasma CETP in mice do not enhance reverse cholesterol transport in vivo but may act on extracellularly located cholesteryl ester.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.