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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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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. |
format | Online Article Text |
id | pubmed-6562066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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