| Enhanced foam cell formation, atherosclerotic lesion development, and inflammation by combined deletion of ABCA1 and SR-BI in Bone marrow-derived cells in LDL receptor knockout mice on western-type diet. | |
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MedLine Citation:
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PMID: 21071707 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: macrophages cannot limit the uptake of lipids and rely on cholesterol efflux mechanisms for maintaining cellular cholesterol homeostasis. Important mediators of macrophage cholesterol efflux are ATP-binding cassette transporter 1 (ABCA1), which mediates the efflux of cholesterol to lipid-poor apolipoprotein AI, and scavenger receptor class B type I (SR-BI), which promotes efflux to mature high-density lipoprotein. OBJECTIVE: the aim of the present study was to increase the insight into the putative synergistic roles of ABCA1 and SR-BI in foam cell formation and atherosclerosis. METHODS AND RESULTS: low-density lipoprotein receptor knockout (LDLr KO) mice were transplanted with bone marrow from ABCA1/SR-BI double knockout mice, the respective single knockouts, or wild-type littermates. Serum cholesterol levels were lower in ABCA1/SR-BI double knockout transplanted animals, as compared to the single knockout and wild-type transplanted animals on Western-type diet. Despite the lower serum cholesterol levels, massive foam cell formation was found in macrophages from spleen and the peritoneal cavity. Interestingly, ABCA1/SR-BI double knockout transplanted animals also showed a major increase in proinflammatory KC (murine interleukin-8) and interleukin-12p40 levels in the circulation. Furthermore, after 10 weeks of Western-type diet feeding, atherosclerotic lesion development in the aortic root was more extensive in the LDLr KO mice reconstituted with ABCA1/SR-BI double knockout bone marrow. CONCLUSIONS: deletion of ABCA1 and SR-BI in bone marrow-derived cells enhances in vivo macrophage foam cell formation and atherosclerotic lesion development in LDLr KO mice on Western diet, indicating that under high dietary lipid conditions, both macrophage ABCA1 and SR-BI contribute significantly to cholesterol homeostasis in the macrophage in vivo and are essential for reducing the risk for atherosclerosis. |
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Authors:
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Ying Zhao; Marieke Pennings; Reeni B Hildebrand; Dan Ye; Laura Calpe-Berdiel; Ruud Out; Martin Kjerrulf; Eva Hurt-Camejo; Albert K Groen; Menno Hoekstra; Wendy Jessup; Giovanna Chimini; Theo J C Van Berkel; Miranda Van Eck |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-11 |
Journal Detail:
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Title: Circulation research Volume: 107 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-14 Completed Date: 2011-01-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: e20-31 Citation Subset: IM |
Affiliation:
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Division of Biopharmaceutics, University Medical Center Groningen, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics* Animals Atherosclerosis / etiology*, genetics, pathology* Bone Marrow / pathology Bone Marrow Transplantation Cholesterol / blood Foam Cells / pathology* Gene Deletion* Homeostasis Inflammation / etiology, genetics Lipid Metabolism Lipoproteins, LDL / genetics Macrophages / pathology Mice Mice, Knockout Scavenger Receptors, Class B / genetics* |
| Chemical | |
Reg. No./Substance:
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0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Lipoproteins, LDL; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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