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APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm

BACKGROUND: High-density lipoproteins (HDL) are a complex mixture of lipids and proteins with vasculoprotective properties. However, HDL components could suffer post-translational modifications (PTMs) under pathological conditions, leading to dysfunctional HDL. We studied whether HDL are modified in...

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Autores principales: Martínez-López, Diego, Camafeita, Emilio, Cedó, Lídia, Roldan-Montero, Raquel, Jorge, Inmaculada, García-Marqués, Fernando, Gómez-Serrano, María, Bonzon-Kulichenko, Elena, Blanco-Vaca, Francisco, Blanco-Colio, Luis Miguel, Michel, Jean-Baptiste, Escola-Gil, Joan Carles, Vázquez, Jesús, Martin-Ventura, Jose Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562066/
https://www.ncbi.nlm.nih.gov/pubmed/30982767
http://dx.doi.org/10.1016/j.ebiom.2019.04.012
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author Martínez-López, Diego
Camafeita, Emilio
Cedó, Lídia
Roldan-Montero, Raquel
Jorge, Inmaculada
García-Marqués, Fernando
Gómez-Serrano, María
Bonzon-Kulichenko, Elena
Blanco-Vaca, Francisco
Blanco-Colio, Luis Miguel
Michel, Jean-Baptiste
Escola-Gil, Joan Carles
Vázquez, Jesús
Martin-Ventura, Jose Luis
author_facet Martínez-López, Diego
Camafeita, Emilio
Cedó, Lídia
Roldan-Montero, Raquel
Jorge, Inmaculada
García-Marqués, Fernando
Gómez-Serrano, María
Bonzon-Kulichenko, Elena
Blanco-Vaca, Francisco
Blanco-Colio, Luis Miguel
Michel, Jean-Baptiste
Escola-Gil, Joan Carles
Vázquez, Jesús
Martin-Ventura, Jose Luis
author_sort Martínez-López, Diego
collection PubMed
description BACKGROUND: High-density lipoproteins (HDL) are a complex mixture of lipids and proteins with vasculoprotective properties. However, HDL components could suffer post-translational modifications (PTMs) under pathological conditions, leading to dysfunctional HDL. We studied whether HDL are modified in abdominal aortic aneurysm (AAA) and the effect on HDL functionality. METHODS: HDL were isolated by ultracentrifugation from AAA tissue (HDL-T) and from plasma of healthy volunteers and then incubated with AAA tissue-conditioned medium (HDL-AAA CM). PTMs from these particles were characterized using Comet-PTM. The ability of HDL-AAA CM for promoting cholesterol efflux was determined ex vivo and in vivo by using J774A.1 [(3)H]cholesterol-labeled mouse macrophages and after injecting [(3)H]cholesterol-labeled mouse macrophages and HDL into the peritoneal cavity of wild-type C57BL/6 mice, respectively. Trp50 and Trp108 oxidized forms of APOA1 in HDL incubated with conditioned-medium of activated neutrophils and in plasma of AAA patients and controls were measured by targeted parallel reaction monitoring. FINDINGS: Oxidation was the most prevalent PTM in apolipoproteins, particularly in APOA1. Trp50 and Trp108 in APOA1 were the residues most clearly affected by oxidation in HDL-T and in HDL-AAA CM, when compared to their controls. In addition, cholesterol efflux was decreased in macrophages incubated with HDL-AAA CM in vitro and a decreased macrophage-to-serum reverse cholesterol transport was also observed in mice injected with HDL-AAA CM. Finally, both oxidized Trp50 and Trp108 forms of APOA1 were increased in HDL incubated with conditioned-medium of activated neutrophils and in plasma of AAA patients in relation to controls. INTERPRETATION: Oxidative modifications of HDL present in AAA tissue and plasma were closely associated with the loss of vasculoprotective properties of HDL in AAA. FUND: MINECO, ISCiii-FEDER, CIBERDEM, CIBERCV and LA CAIXA.
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spelling pubmed-65620662019-06-17 APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm Martínez-López, Diego Camafeita, Emilio Cedó, Lídia Roldan-Montero, Raquel Jorge, Inmaculada García-Marqués, Fernando Gómez-Serrano, María Bonzon-Kulichenko, Elena Blanco-Vaca, Francisco Blanco-Colio, Luis Miguel Michel, Jean-Baptiste Escola-Gil, Joan Carles Vázquez, Jesús Martin-Ventura, Jose Luis EBioMedicine Research paper BACKGROUND: High-density lipoproteins (HDL) are a complex mixture of lipids and proteins with vasculoprotective properties. However, HDL components could suffer post-translational modifications (PTMs) under pathological conditions, leading to dysfunctional HDL. We studied whether HDL are modified in abdominal aortic aneurysm (AAA) and the effect on HDL functionality. METHODS: HDL were isolated by ultracentrifugation from AAA tissue (HDL-T) and from plasma of healthy volunteers and then incubated with AAA tissue-conditioned medium (HDL-AAA CM). PTMs from these particles were characterized using Comet-PTM. The ability of HDL-AAA CM for promoting cholesterol efflux was determined ex vivo and in vivo by using J774A.1 [(3)H]cholesterol-labeled mouse macrophages and after injecting [(3)H]cholesterol-labeled mouse macrophages and HDL into the peritoneal cavity of wild-type C57BL/6 mice, respectively. Trp50 and Trp108 oxidized forms of APOA1 in HDL incubated with conditioned-medium of activated neutrophils and in plasma of AAA patients and controls were measured by targeted parallel reaction monitoring. FINDINGS: Oxidation was the most prevalent PTM in apolipoproteins, particularly in APOA1. Trp50 and Trp108 in APOA1 were the residues most clearly affected by oxidation in HDL-T and in HDL-AAA CM, when compared to their controls. In addition, cholesterol efflux was decreased in macrophages incubated with HDL-AAA CM in vitro and a decreased macrophage-to-serum reverse cholesterol transport was also observed in mice injected with HDL-AAA CM. Finally, both oxidized Trp50 and Trp108 forms of APOA1 were increased in HDL incubated with conditioned-medium of activated neutrophils and in plasma of AAA patients in relation to controls. INTERPRETATION: Oxidative modifications of HDL present in AAA tissue and plasma were closely associated with the loss of vasculoprotective properties of HDL in AAA. FUND: MINECO, ISCiii-FEDER, CIBERDEM, CIBERCV and LA CAIXA. Elsevier 2019-04-11 /pmc/articles/PMC6562066/ /pubmed/30982767 http://dx.doi.org/10.1016/j.ebiom.2019.04.012 Text en © 2019 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Martínez-López, Diego
Camafeita, Emilio
Cedó, Lídia
Roldan-Montero, Raquel
Jorge, Inmaculada
García-Marqués, Fernando
Gómez-Serrano, María
Bonzon-Kulichenko, Elena
Blanco-Vaca, Francisco
Blanco-Colio, Luis Miguel
Michel, Jean-Baptiste
Escola-Gil, Joan Carles
Vázquez, Jesús
Martin-Ventura, Jose Luis
APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm
title APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm
title_full APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm
title_fullStr APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm
title_full_unstemmed APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm
title_short APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm
title_sort apoa1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562066/
https://www.ncbi.nlm.nih.gov/pubmed/30982767
http://dx.doi.org/10.1016/j.ebiom.2019.04.012
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