HDL biology
CETP expression boosts macrophage reverse cholesterol transport in mice via the LDL receptor pathway (Circulation 2007)
Original title: Expression of cholesteryl ester transfer protein in mice promotes macrophage reverse cholesterol transport
Using an AAV8 liver-specific vector to stably express human CETP in mice, which naturally lack the protein, this study tested effects on macrophage reverse cholesterol transport (RCT) via a validated in vivo assay tracking fecal excretion of radiolabeled cholesterol from injected macrophages. In apobec-1-null mice, CETP expression lowered plasma HDL-cholesterol but significantly increased fecal sterol excretion. In LDL-receptor/apobec-1 double-null mice, CETP expression lowered HDL-cholesterol but had no effect on fecal sterol excretion, showing the RCT-promoting effect requires the LDL receptor. In SR-BI-null mice, CETP expression lowered HDL-cholesterol and significantly increased fecal sterol excretion, restoring RCT that SR-BI deficiency normally impairs.
Original abstract
Background: Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from high-density lipoproteins to apolipoprotein (apo) B-containing lipoproteins and in humans plays an important role in lipoprotein metabolism. However, the role that CETP plays in mediation of reverse cholesterol transport (RCT) remains unclear. We used a validated in vivo assay of macrophage RCT to test the effect of CETP expression in mice (which naturally lack CETP) on macrophage RCT, including in mice that lack the low-density lipoprotein receptor or the scavenger receptor class B, type I.
Method And Results: A vector based on adeno-associated virus serotype 8 (AAV8) with a liver-specific thyroglobulin promoter was used to stably express human CETP in livers of mice and was compared with an AAV8-lacZ control vector. The RCT assay was performed 4 weeks after vector injection and involved the intraperitoneal injection of acetylated low-density lipoprotein cholesterol-loaded and 3H-cholesterol-labeled J774 macrophages in mice with plasma sampling at several time points, liver and bile sampling at 48 hours, and continuous fecal collection to measure 3H-sterol as an integrated readout of macrophage RCT. In apobec-1-null mice, CETP expression reduced plasma high-density lipoprotein cholesterol levels but significantly increased fecal 3H-sterol excretion. In low-density lipoprotein receptor/apobec-1 double-null mice, CETP expression reduced high-density lipoprotein cholesterol levels and had no effect on fecal 3H-sterol excretion. Finally, in scavenger receptor class B, type I-null mice, CETP expression reduced high-density lipoprotein cholesterol levels and significantly increased fecal 3H-sterol excretion.
Conclusion: The present results demonstrate that CETP expression promotes macrophage RCT in mice, that this effect is dependent on the low-density lipoprotein receptor, and that CETP expression restores to normal the impaired RCT in mice deficient in scavenger receptor class B, type I.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.