| Macrophage ABCA5 deficiency influences cellular cholesterol efflux and increases susceptibility to atherosclerosis in female LDLr knockout mice. | |
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MedLine Citation:
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PMID: 20382126 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: To determine the role of macrophage ATP-binding cassette transporter A5 (ABCA5) in cellular cholesterol homeostasis and atherosclerotic lesion development. METHODS AND RESULTS: Chimeras with dysfunctional macrophage ABCA5 (ABCA5(-M/-M)) were generated by transplantation of bone marrow from ABCA5 knockout (ABCA5(-/-)) mice into irradiated LDLr(-/-) mice. In vitro, bone marrow-derived macrophages from ABCA5(-M/-M) chimeras exhibited a 29% (P<0.001) decrease in cholesterol efflux to HDL, whereas a 21% (P=0.07) increase in cholesterol efflux to apoA-I was observed. Interestingly, expression of ABCA1, but not ABCG1, was up-regulated in absence of functional ABCA5 in macrophages. To induce atherosclerosis, the transplanted LDLr(-/-) mice were fed a high-cholesterol Western-type diet (WTD) for 6, 10, or 18weeks, allowing analysis of effects on initial as well as advanced lesion development. Atherosclerosis development was not affected in male ABCA5(-M/-M) chimeras after 6, 10, and 18weeks WTD feeding. However, female ABCA5(-M/-M) chimeras did develop significantly (P<0.05) larger aortic root lesions as compared with female controls after 6 and 10weeks WTD feeding. CONCLUSIONS: ABCA5 influences macrophage cholesterol efflux, and selective disruption of ABCA5 in macrophages leads to increased atherosclerotic lesion development in female LDLr(-/-) mice. |
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Authors:
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Dan Ye; Illiana Meurs; Megumi Ohigashi; Laura Calpe-Berdiel; Kim L L Habets; Ying Zhao; Yoshiyuki Kubo; Akihito Yamaguchi; Theo J C Van Berkel; Tsuyoshi Nishi; Miranda Van Eck |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-09 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 395 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-10 Completed Date: 2010-06-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 387-94 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Biopharmaceutics, LACDR, Leiden University, The Netherlands. y.dan@lacdr.leidenuniv.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics,
metabolism* Animals Atherosclerosis / metabolism* Cholesterol / genetics, metabolism* Female Lipids / blood Macrophages / metabolism* Male Mice Mice, Knockout Receptors, LDL / genetics |
| Chemical | |
Reg. No./Substance:
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0/ABCA5 protein, mouse; 0/ATP-Binding Cassette Transporters; 0/Lipids; 0/Receptors, LDL; 57-88-5/Cholesterol |
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