Document Detail


Macrophage ABCA5 deficiency influences cellular cholesterol efflux and increases susceptibility to atherosclerosis in female LDLr knockout mice.
MedLine Citation:
PMID:  20382126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-09
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  395     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-10     Completed Date:  2010-06-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  387-94     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Affiliation:
Division of Biopharmaceutics, LACDR, Leiden University, The Netherlands. y.dan@lacdr.leidenuniv.nl
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Animals
Atherosclerosis / metabolism*
Cholesterol / genetics,  metabolism*
Female
Lipids / blood
Macrophages / metabolism*
Male
Mice
Mice, Knockout
Receptors, LDL / genetics
Chemical
Reg. No./Substance:
0/ABCA5 protein, mouse; 0/ATP-Binding Cassette Transporters; 0/Lipids; 0/Receptors, LDL; 57-88-5/Cholesterol

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