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Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells

Arterial foam cells are central players of atherogenesis. Cholesterol acceptors, apolipoprotein A-I (apoA-I) and high-density lipoprotein (HDL), take up cholesterol and phospholipids effluxed from foam cells into the circulation. Due to the high abundance of cholesterol in foam cells, most previous...

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Autores principales: Paul, Antoni, Lydic, Todd A., Hogan, Ryan, Goo, Young-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695943/
https://www.ncbi.nlm.nih.gov/pubmed/31382484
http://dx.doi.org/10.3390/ijms20153784
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author Paul, Antoni
Lydic, Todd A.
Hogan, Ryan
Goo, Young-Hwa
author_facet Paul, Antoni
Lydic, Todd A.
Hogan, Ryan
Goo, Young-Hwa
author_sort Paul, Antoni
collection PubMed
description Arterial foam cells are central players of atherogenesis. Cholesterol acceptors, apolipoprotein A-I (apoA-I) and high-density lipoprotein (HDL), take up cholesterol and phospholipids effluxed from foam cells into the circulation. Due to the high abundance of cholesterol in foam cells, most previous studies focused on apoA-I/HDL-mediated free cholesterol (FC) transport. However, recent lipidomics of human atherosclerotic plaques also identified that oxidized sterols (oxysterols) and non-sterol lipid species accumulate as atherogenesis progresses. While it is known that these lipids regulate expression of pro-inflammatory genes linked to plaque instability, how cholesterol acceptors impact the foam cell lipidome, particularly oxysterols and non-sterol lipids, remains unexplored. Using lipidomics analyses, we found cholesterol acceptors remodel foam cell lipidomes. Lipid subclass analyses revealed various oxysterols, sphingomyelins, and ceramides, species uniquely enriched in human plaques were significantly reduced by cholesterol acceptors, especially by apoA-I. These results indicate that the function of lipid-poor apoA-I is not limited to the efflux of cholesterol and phospholipids but suggest that apoA-I serves as a major regulator of the foam cell lipidome and might play an important role in reducing multiple lipid species involved in the pathogenesis of atherosclerosis.
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spelling pubmed-66959432019-09-05 Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells Paul, Antoni Lydic, Todd A. Hogan, Ryan Goo, Young-Hwa Int J Mol Sci Article Arterial foam cells are central players of atherogenesis. Cholesterol acceptors, apolipoprotein A-I (apoA-I) and high-density lipoprotein (HDL), take up cholesterol and phospholipids effluxed from foam cells into the circulation. Due to the high abundance of cholesterol in foam cells, most previous studies focused on apoA-I/HDL-mediated free cholesterol (FC) transport. However, recent lipidomics of human atherosclerotic plaques also identified that oxidized sterols (oxysterols) and non-sterol lipid species accumulate as atherogenesis progresses. While it is known that these lipids regulate expression of pro-inflammatory genes linked to plaque instability, how cholesterol acceptors impact the foam cell lipidome, particularly oxysterols and non-sterol lipids, remains unexplored. Using lipidomics analyses, we found cholesterol acceptors remodel foam cell lipidomes. Lipid subclass analyses revealed various oxysterols, sphingomyelins, and ceramides, species uniquely enriched in human plaques were significantly reduced by cholesterol acceptors, especially by apoA-I. These results indicate that the function of lipid-poor apoA-I is not limited to the efflux of cholesterol and phospholipids but suggest that apoA-I serves as a major regulator of the foam cell lipidome and might play an important role in reducing multiple lipid species involved in the pathogenesis of atherosclerosis. MDPI 2019-08-02 /pmc/articles/PMC6695943/ /pubmed/31382484 http://dx.doi.org/10.3390/ijms20153784 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Paul, Antoni
Lydic, Todd A.
Hogan, Ryan
Goo, Young-Hwa
Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells
title Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells
title_full Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells
title_fullStr Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells
title_full_unstemmed Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells
title_short Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells
title_sort cholesterol acceptors regulate the lipidome of macrophage foam cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695943/
https://www.ncbi.nlm.nih.gov/pubmed/31382484
http://dx.doi.org/10.3390/ijms20153784
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