| High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation. | |
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MedLine Citation:
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PMID: 22833685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Macrophage foam cells are a defining pathologic feature of atherosclerotic lesions. Recent studies have demonstrated that at high concentrations associated with hypercholesterolemia, native LDL induces macrophage lipid accumulation. LDL particles are taken up by macrophages as part of bulk fluid pinocytosis. However, the uptake and metabolism of cholesterol from native LDL during foam cell formation has not been clearly defined. Previous reports have suggested that selective cholesteryl ester (CE) uptake might contribute to cholesterol uptake from LDL independently of particle endocytosis. In this study we demonstrate that the majority of macrophage LDL-derived cholesterol is acquired by selective CE uptake in excess of LDL pinocytosis and degradation. Macrophage selective CE uptake does not saturate at high LDL concentrations and is not down-regulated during cholesterol accumulation. In contrast to CE uptake, macrophages exhibit little selective uptake of free cholesterol (FC) from LDL. Following selective uptake from LDL, CE is rapidly hydrolyzed by a novel chloroquine-sensitive pathway. FC released from LDL-derived CE hydrolysis is largely effluxed from cells but also is subject to ACAT-mediated reesterification. These results indicate that selective CE uptake plays a major role in macrophage metabolism of LDL. |
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Authors:
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Jason M Meyer; Ailing Ji; Lei Cai; Deneys R van der Westhuyzen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-07-25 |
Journal Detail:
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Title: Journal of lipid research Volume: 53 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-09-07 Completed Date: 2013-01-29 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 2081-91 Citation Subset: IM |
Affiliation:
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Department of Veterans Affairs Medical Center, Lexington, KY 40502, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cholesterol Esters / metabolism* Cholesterol, LDL / metabolism* Foam Cells / metabolism* Humans Macrophages / metabolism* Mice Mice, Inbred Strains Pinocytosis |
| Grant Support | |
ID/Acronym/Agency:
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5P20RR-021954-05/RR/NCRR NIH HHS; 8P20GM-103527-05/GM/NIGMS NIH HHS; P01-HL-086670-04/HL/NHLBI NIH HHS; T32-HL-072743/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol Esters; 0/Cholesterol, LDL |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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