In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 30, No. 7 ( 2010-07), p. 1439-1445
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. Conclusion— 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.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/ATVBAHA.110.205153
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2010
detail.hit.zdb_id:
1494427-3
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