| Overexpression of STARD3 in human monocyte/macrophages induces an anti-atherogenic lipid phenotype. | |
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MedLine Citation:
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PMID: 20491656 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dysregulated macrophage cholesterol homoeostasis lies at the heart of early and developing atheroma, and removal of excess cholesterol from macrophage foam cells, by efficient transport mechanisms, is central to stabilization and regression of atherosclerotic lesions. The present study demonstrates that transient overexpression of STARD3 {START [StAR (steroidogenic acute regulatory protein)-related lipid transfer] domain 3; also known as MLN64 (metastatic lymph node 64)}, an endosomal cholesterol transporter and member of the 'START' family of lipid trafficking proteins, induces significant increases in macrophage ABCA1 (ATP-binding cassette transporter A1) mRNA and protein, enhances [(3)H]cholesterol efflux to apo (apolipoprotein) AI, and reduces biosynthesis of cholesterol, cholesteryl ester, fatty acids, triacylglycerol and phospholipids from [(14)C]acetate, compared with controls. Notably, overexpression of STARD3 prevents increases in cholesterol esterification in response to acetylated LDL (low-density lipoprotein), blocking cholesteryl ester deposition. Thus enhanced endosomal trafficking via STARD3 induces an anti-atherogenic macrophage lipid phenotype, positing a potentially therapeutic strategy. |
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Authors:
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Faye Borthwick; Anne-Marie Allen; Janice M Taylor; Annette Graham |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-22 |
Journal Detail:
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Title: Clinical science (London, England : 1979) Volume: 119 ISSN: 1470-8736 ISO Abbreviation: Clin. Sci. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-06-25 Completed Date: 2010-09-16 Revised Date: 2010-09-30 |
Medline Journal Info:
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Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 265-72 Citation Subset: IM |
Affiliation:
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Vascular Biology Group, Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aorta
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metabolism Atherosclerosis / metabolism* Carrier Proteins / biosynthesis*, genetics Cells, Cultured Foam Cells / metabolism Gene Expression Regulation / physiology Humans Lipid Metabolism / physiology* Macrophages / metabolism* Membrane Proteins / biosynthesis*, genetics Monocytes / metabolism* Phenotype Polymerase Chain Reaction / methods RNA, Messenger / genetics |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Membrane Proteins; 0/RNA, Messenger; 0/STARD3 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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