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Título: | APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm |
Autor: | Martínez-López, Diego; Camafeita, Emilio; Cedó, Lídia; Roldan-Montero, Raquel; Jorge, Inmaculada CSIC ORCID; García-Marqués, Fernando; Gómez-Serrano, María CSIC ORCID; Bonzón-Kulichenko, Elena CSIC ORCID; Blanco-Vaca, Francisco; Blanco-Colio, Luis Miguel; Michel, Jean-Baptiste; Escolà-Gil, Joan Carles; Vázquez, Jesús CSIC ORCID CVN; Martín-Ventura, Jose Luis | Palabras clave: | Abdominal aortic aneurysm HDL Oxidative stress Proteomics Cholesterol efflux Biomarkers |
Fecha de publicación: | may-2019 | Editor: | Elsevier BV | Citación: | EBioMedicine 43: 43-53 (2019) | Resumen: | 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 [H]cholesterol-labeled mouse macrophages and after injecting [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. | Versión del editor: | http://dx.doi.org/10.1016/j.ebiom.2019.04.012 | URI: | http://hdl.handle.net/10261/201287 | DOI: | 10.1016/j.ebiom.2019.04.012 | Identificadores: | doi: 10.1016/j.ebiom.2019.04.012 e-issn: 2352-3964 |
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