HDL biology
Human CETP transgene boosts macrophage reverse cholesterol transport in mice, but cannot rescue PLTP deficiency (J Physiol Biochem 2021)
Original title: Human cholesteryl ester transport protein transgene promotes macrophage reverse cholesterol transport in C57BL/6 mice and phospholipid transfer protein gene knockout mice
In mice carrying a human CETP transgene (CETP-tg), crossed with phospholipid transfer protein (PLTP) knockout animals, researchers tracked reverse cholesterol transport (RCT) using radiolabelled cholesterol-laden macrophages. CETP-tg mice showed significantly increased transport of cholesterol from macrophages to plasma and liver, and higher faecal excretion, compared with wild-type littermates, and this RCT-improving effect was similar in PLTP knockout mice. CETP-tg did not alter expression of RCT-related proteins such as the low-density lipoprotein receptor; the benefit was instead linked to lower levels of oxidised lipids and CETP-mediated lipid transport itself. The findings show CETP transgene expression improves RCT in mice, but cannot compensate for the loss of PLTP.
Original abstract
Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) belong to the same gene family. Liver-specific expression of CETP improves reverse cholesterol transport (RCT) and PLTP knockout (KO) decreases RCT in mice. In this study, we investigate the effect of CETP transgene (CETP-tg) on RCT and whether CETP-tg can partially restore RCT efficiency in PLTP KO mice. Several rounds of crossing were carried out to produce colonies of wild type (WT), CETP-tg, PLTP KO, and CETP-tg × PLTP KO mice were obtained after several generations of reproduction. The efficiency of RCT was detected using [3H]-cholesterol-laden macrophages, and the underlying mechanisms were investigated by multiple techniques. Our data demonstrated that CETP-tg significantly increased the transport rate of [3H]-cholesterol from macrophages to plasma and liver, and finally the excretion through feces compared to the WT littermates. The RCT improving effect of CETP-tg was similar in PLTPKO mice. Furthermore, CETP-tg did not affect the expression of RCT-related proteins, such as low-density lipoprotein receptor. The mechanisms of improving RCT may be attributed to the low level of oxidized lipids in CETP-tg mouse and CETP-mediated lipid transport. Collectively, CETP-tg improves RCT in mice, and CETP can not compensate for PLTP deficiency.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.