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Effects of copper sulfate-oxidized or myeloperoxidase-modified LDL on lipid loading and programmed cell death in macrophages under hypoxia

Atheromatous plaques contain heavily lipid-loaded macrophages that die, hence generating the necrotic core of these plaques. Since plaque instability and rupture is often correlated with a large necrotic core, it is important to understand the mechanisms underlying foam cell death. Furthermore, macr...

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Autores principales: Vlaminck, Benoit, Calay, Damien, Genin, Marie, Sauvage, Aude, Ninane, Noelle, Zouaoui Boudjeltia, Karim, Raes, Martine, Michiels, Carine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045064/
https://www.ncbi.nlm.nih.gov/pubmed/27774474
http://dx.doi.org/10.2147/HP.S65242
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author Vlaminck, Benoit
Calay, Damien
Genin, Marie
Sauvage, Aude
Ninane, Noelle
Zouaoui Boudjeltia, Karim
Raes, Martine
Michiels, Carine
author_facet Vlaminck, Benoit
Calay, Damien
Genin, Marie
Sauvage, Aude
Ninane, Noelle
Zouaoui Boudjeltia, Karim
Raes, Martine
Michiels, Carine
author_sort Vlaminck, Benoit
collection PubMed
description Atheromatous plaques contain heavily lipid-loaded macrophages that die, hence generating the necrotic core of these plaques. Since plaque instability and rupture is often correlated with a large necrotic core, it is important to understand the mechanisms underlying foam cell death. Furthermore, macrophages within the plaque are associated with hypoxic areas but little is known about the effect of low oxygen partial pressure on macrophage death. The aim of this work was to unravel macrophage death mechanisms induced by oxidized low-density lipoproteins (LDL) both under normoxia and hypoxia. Differentiated macrophages were incubated in the presence of native, copper sulfate-oxidized, or myeloperoxidase-modified LDL. The unfolded protein response, apoptosis, and autophagy were then investigated. The unfolded protein response and autophagy were triggered by myeloperoxidase-modified LDL and, to a larger extent, by copper sulfate-oxidized LDL. Electron microscopy observations showed that oxidized LDL induced excessive autophagy and apoptosis under normoxia, which were less marked under hypoxia. Myeloperoxidase-modified LDL were more toxic and induced a higher level of apoptosis. Hypoxia markedly decreased apoptosis and cell death, as marked by caspase activation. In conclusion, the cell death pathways induced by copper sulfate-oxidized and myeloperoxidase-modified LDL are different and are differentially modulated by hypoxia.
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spelling pubmed-50450642016-10-21 Effects of copper sulfate-oxidized or myeloperoxidase-modified LDL on lipid loading and programmed cell death in macrophages under hypoxia Vlaminck, Benoit Calay, Damien Genin, Marie Sauvage, Aude Ninane, Noelle Zouaoui Boudjeltia, Karim Raes, Martine Michiels, Carine Hypoxia (Auckl) Original Research Atheromatous plaques contain heavily lipid-loaded macrophages that die, hence generating the necrotic core of these plaques. Since plaque instability and rupture is often correlated with a large necrotic core, it is important to understand the mechanisms underlying foam cell death. Furthermore, macrophages within the plaque are associated with hypoxic areas but little is known about the effect of low oxygen partial pressure on macrophage death. The aim of this work was to unravel macrophage death mechanisms induced by oxidized low-density lipoproteins (LDL) both under normoxia and hypoxia. Differentiated macrophages were incubated in the presence of native, copper sulfate-oxidized, or myeloperoxidase-modified LDL. The unfolded protein response, apoptosis, and autophagy were then investigated. The unfolded protein response and autophagy were triggered by myeloperoxidase-modified LDL and, to a larger extent, by copper sulfate-oxidized LDL. Electron microscopy observations showed that oxidized LDL induced excessive autophagy and apoptosis under normoxia, which were less marked under hypoxia. Myeloperoxidase-modified LDL were more toxic and induced a higher level of apoptosis. Hypoxia markedly decreased apoptosis and cell death, as marked by caspase activation. In conclusion, the cell death pathways induced by copper sulfate-oxidized and myeloperoxidase-modified LDL are different and are differentially modulated by hypoxia. Dove Medical Press 2014-09-23 /pmc/articles/PMC5045064/ /pubmed/27774474 http://dx.doi.org/10.2147/HP.S65242 Text en © 2014 Vlaminck et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Vlaminck, Benoit
Calay, Damien
Genin, Marie
Sauvage, Aude
Ninane, Noelle
Zouaoui Boudjeltia, Karim
Raes, Martine
Michiels, Carine
Effects of copper sulfate-oxidized or myeloperoxidase-modified LDL on lipid loading and programmed cell death in macrophages under hypoxia
title Effects of copper sulfate-oxidized or myeloperoxidase-modified LDL on lipid loading and programmed cell death in macrophages under hypoxia
title_full Effects of copper sulfate-oxidized or myeloperoxidase-modified LDL on lipid loading and programmed cell death in macrophages under hypoxia
title_fullStr Effects of copper sulfate-oxidized or myeloperoxidase-modified LDL on lipid loading and programmed cell death in macrophages under hypoxia
title_full_unstemmed Effects of copper sulfate-oxidized or myeloperoxidase-modified LDL on lipid loading and programmed cell death in macrophages under hypoxia
title_short Effects of copper sulfate-oxidized or myeloperoxidase-modified LDL on lipid loading and programmed cell death in macrophages under hypoxia
title_sort effects of copper sulfate-oxidized or myeloperoxidase-modified ldl on lipid loading and programmed cell death in macrophages under hypoxia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045064/
https://www.ncbi.nlm.nih.gov/pubmed/27774474
http://dx.doi.org/10.2147/HP.S65242
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