HDL biology
CETP restores HDL cholesterol in SR-BI-deficient mice but fails to prevent atherosclerosis (Arterioscler Thromb Vasc Biol 2010)
Original title: Restoration of high-density lipoprotein levels by cholesteryl ester transfer protein expression in scavenger receptor class B type I (SR-BI) knockout mice does not normalize pathologies associated with SR-BI deficiency
Introducing human CETP into scavenger receptor SR-BI knockout mice lowered plasma HDL-cholesterol 1.8-fold on a chow diet (P<0.001) and 1.6-fold on a Western-type diet (P<0.01), and partially normalized the abnormally large HDL particles seen in SR-BI-deficient mice. Despite restoring HDL-C levels, CETP expression did not reduce atherosclerotic lesion development, and failed to normalize elevated VLDL-cholesterol, the free-to-total cholesterol ratio, oxidative status, female infertility, reticulocytosis, thrombocytopenia, or impaired platelet aggregation associated with SR-BI deficiency, indicating SR-BI's pathology is not simply a consequence of changes in the HDL pool.
Original abstract
Objective: Disruption of scavenger receptor class B type I (SR-BI) in mice impairs high-density lipoprotein (HDL)-cholesterol (HDL-C) delivery to the liver and induces susceptibility to atherosclerosis. In this study, it was investigated whether introduction of cholesteryl ester transfer protein (CETP) can normalize HDL-C transport to the liver and reduce atherosclerosis in SR-BI knockout (KO) mice.
Methods And Results: Expression of human CETP in SR-BI(KO) mice resulted in decreased plasma HDL-C levels, both on chow diet (1.8-fold, P<0.001) and on challenge with Western-type diet (1.6-fold, P<0.01). Furthermore, the presence of CETP partially normalized the abnormally large HDL particles observed in SR-BI(KO) mice. Unexpectedly, expression of CETP in SR-BI(KO) mice did not reduce atherosclerotic lesion development, probably because of consequences of SR-BI deficiency, including the persistence of higher VLDL-cholesterol (VLDL-C) levels, unchanged elevated free cholesterol/total cholesterol ratio, and the increased oxidative status of the animals. In addition, CETP expression did not normalize other characteristics of SR-BI deficiency, including female infertility, reticulocytosis, thrombocytopenia, and impaired platelet aggregation.
Conclusions: CETP restores HDL-C levels in SR-BI(KO) mice, but it does not change the susceptibility to atherosclerosis and other typical characteristics that are associated with SR-BI disruption. This may indicate that the pathophysiology of SR-BI deficiency is not a direct consequence of changes in the HDL pool.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.