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High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation
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 pin...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435541/ https://www.ncbi.nlm.nih.gov/pubmed/22833685 http://dx.doi.org/10.1194/jlr.M026534 |
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author | Meyer, Jason M. Ji, Ailing Cai, Lei van der Westhuyzen, Deneys R. |
author_facet | Meyer, Jason M. Ji, Ailing Cai, Lei van der Westhuyzen, Deneys R. |
author_sort | Meyer, Jason M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3435541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-34355412013-10-01 High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation Meyer, Jason M. Ji, Ailing Cai, Lei van der Westhuyzen, Deneys R. J Lipid Res Research Articles 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. The American Society for Biochemistry and Molecular Biology 2012-10 /pmc/articles/PMC3435541/ /pubmed/22833685 http://dx.doi.org/10.1194/jlr.M026534 Text en http://creativecommons.org/licenses/by/2.5/ Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Research Articles Meyer, Jason M. Ji, Ailing Cai, Lei van der Westhuyzen, Deneys R. High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation |
title | High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation |
title_full | High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation |
title_fullStr | High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation |
title_full_unstemmed | High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation |
title_short | High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation |
title_sort | high-capacity selective uptake of cholesteryl ester from native ldl during macrophage foam cell formation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435541/ https://www.ncbi.nlm.nih.gov/pubmed/22833685 http://dx.doi.org/10.1194/jlr.M026534 |
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