| 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. | |
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MedLine Citation:
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PMID: 20431066 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Reeni B Hildebrand; Bart Lammers; Illiana Meurs; Suzanne J A Korporaal; Willeke De Haan; Ying Zhao; J Kar Kruijt; Domenico Praticò; Alinda W M Schimmel; Adriaan G Holleboom; Menno Hoekstra; Jan Albert Kuivenhoven; Theo J C Van Berkel; Patrick C N Rensen; Miranda Van Eck |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-29 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-17 Completed Date: 2010-07-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1439-45 Citation Subset: IM |
Affiliation:
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Leiden/Amsterdam Center for Drug Research, Division of Biopharmaceutics, Leiden, the Netherlands. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / genetics, metabolism*, pathology Cholesterol Ester Transfer Proteins / genetics, metabolism* Cholesterol, HDL / blood* Cholesterol, LDL / blood Cholesterol, VLDL / blood Disease Models, Animal Female Humans Infertility, Female / genetics, metabolism Kinetics Liver / metabolism* Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Oxidative Stress Particle Size Platelet Aggregation / genetics Platelet Count Reticulocytosis / genetics Scavenger Receptors, Class B / deficiency*, genetics |
| Chemical | |
Reg. No./Substance:
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0/CETP protein, human; 0/Cholesterol Ester Transfer Proteins; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Cholesterol, VLDL; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B |
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