Cargando…

Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion

Myocardial ischemia is associated with intracellular accumulation of lipids and increased depots of myocardial lipids are linked to decreased heart function. Despite investigations in cell culture and animal models, there is little data available on where in the heart the lipids accumulate after myo...

Descripción completa

Detalles Bibliográficos
Autores principales: Drevinge, Christina, Karlsson, Lars O., Ståhlman, Marcus, Larsson, Thomas, Perman Sundelin, Jeanna, Grip, Lars, Andersson, Linda, Borén, Jan, Levin, Malin C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637450/
https://www.ncbi.nlm.nih.gov/pubmed/23637933
http://dx.doi.org/10.1371/journal.pone.0061942
_version_ 1782267476055162880
author Drevinge, Christina
Karlsson, Lars O.
Ståhlman, Marcus
Larsson, Thomas
Perman Sundelin, Jeanna
Grip, Lars
Andersson, Linda
Borén, Jan
Levin, Malin C.
author_facet Drevinge, Christina
Karlsson, Lars O.
Ståhlman, Marcus
Larsson, Thomas
Perman Sundelin, Jeanna
Grip, Lars
Andersson, Linda
Borén, Jan
Levin, Malin C.
author_sort Drevinge, Christina
collection PubMed
description Myocardial ischemia is associated with intracellular accumulation of lipids and increased depots of myocardial lipids are linked to decreased heart function. Despite investigations in cell culture and animal models, there is little data available on where in the heart the lipids accumulate after myocardial ischemia and which lipid species that accumulate. The aim of this study was to investigate derangements of lipid metabolism that are associated with myocardial ischemia in a porcine model of ischemia and reperfusion. The large pig heart enables the separation of the infarct area with irreversible injury from the area at risk with reversible injury and the unaffected control area. The surviving myocardium bordering the infarct is exposed to mild ischemia and is stressed, but remains viable. We found that cholesteryl esters accumulated in the infarct area as well as in the bordering myocardium. In addition, we found that expression of the low density lipoprotein receptor (LDLr) and the low density lipoprotein receptor-related protein 1 (LRP1) was up-regulated, suggesting that choleteryl ester uptake is mediated via these receptors. Furthermore, we found increased ceramide accumulation, inflammation and endoplasmatic reticulum (ER) stress in the infarcted area of the pig heart. In addition, we found increased levels of inflammation and ER stress in the myocardium bordering the infarct area. Our results indicate that lipid accumulation in the heart is one of the metabolic derangements remaining after ischemia, even in the myocardium bordering the infarct area. Normalizing lipid levels in the myocardium after ischemia would likely improve myocardial function and should therefore be considered as a target for treatment.
format Online
Article
Text
id pubmed-3637450
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-36374502013-05-01 Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion Drevinge, Christina Karlsson, Lars O. Ståhlman, Marcus Larsson, Thomas Perman Sundelin, Jeanna Grip, Lars Andersson, Linda Borén, Jan Levin, Malin C. PLoS One Research Article Myocardial ischemia is associated with intracellular accumulation of lipids and increased depots of myocardial lipids are linked to decreased heart function. Despite investigations in cell culture and animal models, there is little data available on where in the heart the lipids accumulate after myocardial ischemia and which lipid species that accumulate. The aim of this study was to investigate derangements of lipid metabolism that are associated with myocardial ischemia in a porcine model of ischemia and reperfusion. The large pig heart enables the separation of the infarct area with irreversible injury from the area at risk with reversible injury and the unaffected control area. The surviving myocardium bordering the infarct is exposed to mild ischemia and is stressed, but remains viable. We found that cholesteryl esters accumulated in the infarct area as well as in the bordering myocardium. In addition, we found that expression of the low density lipoprotein receptor (LDLr) and the low density lipoprotein receptor-related protein 1 (LRP1) was up-regulated, suggesting that choleteryl ester uptake is mediated via these receptors. Furthermore, we found increased ceramide accumulation, inflammation and endoplasmatic reticulum (ER) stress in the infarcted area of the pig heart. In addition, we found increased levels of inflammation and ER stress in the myocardium bordering the infarct area. Our results indicate that lipid accumulation in the heart is one of the metabolic derangements remaining after ischemia, even in the myocardium bordering the infarct area. Normalizing lipid levels in the myocardium after ischemia would likely improve myocardial function and should therefore be considered as a target for treatment. Public Library of Science 2013-04-26 /pmc/articles/PMC3637450/ /pubmed/23637933 http://dx.doi.org/10.1371/journal.pone.0061942 Text en © 2013 Drevinge 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
Drevinge, Christina
Karlsson, Lars O.
Ståhlman, Marcus
Larsson, Thomas
Perman Sundelin, Jeanna
Grip, Lars
Andersson, Linda
Borén, Jan
Levin, Malin C.
Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion
title Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion
title_full Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion
title_fullStr Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion
title_full_unstemmed Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion
title_short Cholesteryl Esters Accumulate in the Heart in a Porcine Model of Ischemia and Reperfusion
title_sort cholesteryl esters accumulate in the heart in a porcine model of ischemia and reperfusion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637450/
https://www.ncbi.nlm.nih.gov/pubmed/23637933
http://dx.doi.org/10.1371/journal.pone.0061942
work_keys_str_mv AT drevingechristina cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion
AT karlssonlarso cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion
AT stahlmanmarcus cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion
AT larssonthomas cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion
AT permansundelinjeanna cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion
AT griplars cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion
AT anderssonlinda cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion
AT borenjan cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion
AT levinmalinc cholesterylestersaccumulateintheheartinaporcinemodelofischemiaandreperfusion