Torcetrapib
Both raising and lowering CETP activity can enhance reverse cholesterol transport, depending on the species and pathway studied (Cardiovasc Res 2008)
Original title: The effect of cholesteryl ester transfer protein overexpression and inhibition on reverse cholesterol transport
Researchers investigated how CETP overexpression or inhibition affects reverse cholesterol transport (RCT). Neither CETP overexpression nor torcetrapib treatment of macrophages or hepatocytes affected cholesterol efflux in vitro, though CETP overexpression stimulated and torcetrapib inhibited HDL cholesteryl ester uptake specifically in hepatocytes. In mice injected with transfected macrophages, cholesterol egress was elevated for ABCA1-transfected but not CETP-transfected cells, while systemic CETP expression via adenoviral infection stimulated cholesterol egress to plasma and liver without changing HDL levels. Torcetrapib did not affect macrophage cholesterol appearing in plasma and liver in mice but inhibited its excretion into feces, whereas in hamsters torcetrapib raised HDL cholesterol, boosted plasma cholesterol efflux capacity, and increased macrophage cholesterol egress to both plasma and feces, showing that both increased and decreased CETP activity can enhance RCT depending on species and pathway.
Original abstract
Aims: Cholesteryl ester transfer protein (CETP) has a well-established role in lipoprotein metabolism, but the effect of its overexpression or inhibition on the efficiency of reverse cholesterol transport (RCT) is unclear.
Methods And Results: Neither overexpression of CETP nor treatment with CETP inhibitor Torcetrapib of RAW 264.7 macrophages or HepG2 hepatocytes affected cholesterol efflux in vitro. Overexpression of CETP or treatment with Torcetrapib, respectively, stimulated or inhibited HDL cholesteryl ester uptake by HepG2 but not by RAW 264.7 cells. When RAW 264.7 cells transfected with CETP or ATP binding cassette transporter A1 (ABCA1) were injected intraperitoneally into mice, cholesterol egress from macrophages was elevated for ABCA1- but not for CETP-transfected macrophages. Systemic expression of CETP in mice by adenoviral infection stimulated egress of cholesterol to plasma and liver without affecting HDL levels. Treatment with Torcetrapib did not affect appearance of macrophage cholesterol in plasma and liver, but inhibited its excretion into feces. Treatment of hamsters with Torcetrapib led to elevation of HDL cholesterol, an increase in the capacity of plasma to support cholesterol efflux, and increased egress of cholesterol from macrophages to plasma and feces in vivo.
Conclusion: Both increased (mice study) and decreased (hamster study) CETP activity could result in enhanced RCT.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.