2026-06-30T00:10:13Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/78512024-09-27T08:13:31Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Martínez-López, Diego author Camafeita, Emilio author Cedó, Lídia author Roldan-Montero, Raquel author Jorge, Inmaculada author Garcia-Marques, Fernando author Gomez-Serrano, Maria author Bonzon-Kulichenko, Elena author Blanco-Vaca, Francisco author Blanco-Colio, Luis Miguel author Michel, Jean-Baptiste author Escola-Gil, Joan Carles author Vazquez, Jesus author Martin-Ventura, Jose Luis author 2019-05 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 [3H]cholesterol-labeled mouse macrophages and after injecting [3H]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. EBioMedicine. 2019; 43:43-53 10.1016/j.ebiom.2019.04.012 2352-3964 23523964 EBioMedicine 30982767 http://hdl.handle.net/20.500.12105/7851 Abdominal aortic aneurysm Biomarkers Cholesterol efflux HDL Oxidative stress Proteomics APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm