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Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins
High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388475/ https://www.ncbi.nlm.nih.gov/pubmed/25849485 http://dx.doi.org/10.1371/journal.pone.0123138 |
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author | Chadwick, Alexandra C. Holme, Rebecca L. Chen, Yiliang Thomas, Michael J. Sorci-Thomas, Mary G. Silverstein, Roy L. Pritchard, Kirkwood A. Sahoo, Daisy |
author_facet | Chadwick, Alexandra C. Holme, Rebecca L. Chen, Yiliang Thomas, Michael J. Sorci-Thomas, Mary G. Silverstein, Roy L. Pritchard, Kirkwood A. Sahoo, Daisy |
author_sort | Chadwick, Alexandra C. |
collection | PubMed |
description | High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway. |
format | Online Article Text |
id | pubmed-4388475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43884752015-04-21 Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins Chadwick, Alexandra C. Holme, Rebecca L. Chen, Yiliang Thomas, Michael J. Sorci-Thomas, Mary G. Silverstein, Roy L. Pritchard, Kirkwood A. Sahoo, Daisy PLoS One Research Article High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway. Public Library of Science 2015-04-07 /pmc/articles/PMC4388475/ /pubmed/25849485 http://dx.doi.org/10.1371/journal.pone.0123138 Text en © 2015 Chadwick et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chadwick, Alexandra C. Holme, Rebecca L. Chen, Yiliang Thomas, Michael J. Sorci-Thomas, Mary G. Silverstein, Roy L. Pritchard, Kirkwood A. Sahoo, Daisy Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins |
title | Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins |
title_full | Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins |
title_fullStr | Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins |
title_full_unstemmed | Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins |
title_short | Acrolein Impairs the Cholesterol Transport Functions of High Density Lipoproteins |
title_sort | acrolein impairs the cholesterol transport functions of high density lipoproteins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388475/ https://www.ncbi.nlm.nih.gov/pubmed/25849485 http://dx.doi.org/10.1371/journal.pone.0123138 |
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