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dc.contributor.author | Rodríguez-Carrio, Javier | |
dc.contributor.author | Cerro-Pardo, Isabel | |
dc.contributor.author | Lindholt, Jes S | |
dc.contributor.author | Bonzon-Kulichenko, Elena | |
dc.contributor.author | Martínez-López, Diego | |
dc.contributor.author | Roldán-Montero, Raquel | |
dc.contributor.author | Escolà-Gil, Joan-Carles | |
dc.contributor.author | Michel, Jean-Baptiste | |
dc.contributor.author | Blanco-Colio, Luis Miguel | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Suárez, Ana | |
dc.contributor.author | Martín-Ventura, José Luis | |
dc.date.accessioned | 2024-06-27T10:19:31Z | |
dc.date.available | 2024-06-27T10:19:31Z | |
dc.date.issued | 2021-10 | |
dc.identifier.citation | Free Radic Biol Med. 2021 Oct:174:171-181. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19880 | |
dc.description.abstract | High Density Lipoprotein (HDL) plays a protective role in abdominal aortic aneurysm (AAA); however, recent findings suggest that oxidative modifications could lead to dysfunctional HDL in AAA. This study aimed at testing the effect of oxidized HDL on aortic lesions and humoral immune responses in a mouse model of AAA induced by elastase, and evaluating whether antibodies against modified HDL can be found in AAA patients. HDL particles were oxidized with malondialdehyde (HDL-MDA) and the changes were studied by biochemical and proteomics approaches. Experimental AAA was induced in mice by elastase perfusion and then mice were treated with HDL-MDA, HDL or vehicle for 14 days. Aortic lesions were studied by histomorphometric analysis. Levels of anti-HDL-MDA IgG antibodies were measured by an in-house immunoassay in the mouse model, in human tissue-supernatants and in plasma samples from the VIVA cohort. HDL oxidation with MDA was confirmed by enhanced susceptibility to diene formation. Proteomics demonstrated the presence of MDA adducts on Lysine residues of HDL proteins, mainly ApoA-I. MDA-modification of HDL abrogated the protective effect of HDL on cultured endothelial cells as well as on AAA dilation in mice. Exposure to HDL-MDA elicited an anti-HDL-MDA IgG response in mice. Anti-HDL-MDA were also detected in tissue-conditioned media from AAA patients, mainly in intraluminal thrombus. Higher plasma levels of anti-HDL-MDA IgG antibodies were found in AAA patients compared to controls. Anti-HDL-MDA levels were associated with smoking and were independent predictors of overall mortality in AAA patients. Overall, MDA-oxidized HDL trigger a specific humoral immune response in mice. Besides, antibodies against HDL-MDA can be detected in tissue and plasma of AAA patients, suggesting its potential use as surrogate stable biomarkers of oxidative stress in AAA. | es_ES |
dc.description.sponsorship | This study was funded by the Spanish MINECO (SAF2016-80843-R, PID2019-106814RB-I00 and PGC2018-097019-B-I00), CAM (Complemento II-CM, S2017/BMD-3673), Fondo de Investigaciones Sanitarias ISCIII-FEDER (PI19/00128, Biobancos RD09/0076/00101, PI16/ 00113 and PT17/0019/0003-ISCIII-SGEFI/ERDF, ProteoRed), and FEDER “Una manera de hacer Europa”. CIBERCV and CIBERDEM are Instituto de Salud Carlos III projects. The work leading to these results has also received funding from “la Caixa” Banking Foundation under the project code HR17-00247. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Aortic Aneurysm, Abdominal | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Disease Models, Animal | es_ES |
dc.subject.mesh | Endothelial Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Immunoglobulin G | es_ES |
dc.subject.mesh | Lipoproteins, HDL | es_ES |
dc.subject.mesh | Malondialdehyde | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.title | Malondialdehyde-modified HDL particles elicit a specific IgG response in abdominal aortic aneurysm. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 34364980 | es_ES |
dc.format.volume | 174 | es_ES |
dc.format.page | 171 | es_ES |
dc.identifier.doi | 10.1016/j.freeradbiomed.2021.08.004 | es_ES |
dc.contributor.funder | Ministerio de Economía, Innovación y Competitividad (España) | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1873-4596 | es_ES |
dc.relation.publisherversion | 10.1016/j.freeradbiomed.2021.08.004 | es_ES |
dc.identifier.journal | Free radical biology & medicine | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2016-80843-R | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-106814RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PGC2018-097019-B-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/S2017/BMD-3673 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PT17/0019/0003-ISCIII-SGEFI/ERDF | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR17-00247 | es_ES |