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dc.contributor.authorNevado, Rosa M 
dc.contributor.authorHamczyk, Magda R. 
dc.contributor.authorGonzalo, Pilar 
dc.contributor.authorAndres-Manzano, Maria J. 
dc.contributor.authorAndres, Vicente 
dc.date.accessioned2020-10-26T08:55:13Z
dc.date.available2020-10-26T08:55:13Z
dc.date.issued2020-10-08
dc.identifier.citationCells. 2020; 9(10):E2252es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11194
dc.description.abstractHutchinson-Gilford progeria syndrome (HGPS) is among the most devastating of the laminopathies, rare genetic diseases caused by mutations in genes encoding nuclear lamina proteins. HGPS patients age prematurely and die in adolescence, typically of atherosclerosis-associated complications. The mechanisms of HGPS-related atherosclerosis are not fully understood due to the scarcity of patient-derived samples and the availability of only one atheroprone mouse model of the disease. Here, we generated a new atherosusceptible model of HGPS by crossing progeroid LmnaG609G/G609G mice, which carry a disease-causing mutation in the Lmna gene, with Ldlr-/- mice, a commonly used preclinical atherosclerosis model. Ldlr-/-LmnaG609G/G609G mice aged prematurely and had reduced body weight and survival. Compared with control mice, Ldlr-/-LmnaG609G/G609G mouse aortas showed a higher atherosclerosis burden and structural abnormalities typical of HGPS patients, including vascular smooth muscle cell depletion in the media, adventitial thickening, and elastin structure alterations. Atheromas of Ldlr-/-LmnaG609G/G609G mice had features of unstable plaques, including the presence of erythrocytes and iron deposits and reduced smooth muscle cell and collagen content. Ldlr-/-LmnaG609G/G609G mice faithfully recapitulate vascular features found in patients and thus provide a new tool for studying the mechanisms of HGPS-related atherosclerosis and for testing therapies.es_ES
dc.description.sponsorshipWork in Andrés’ laboratory is supported by the Spanish Ministerio de Ciencia e Innovación (MCIN) (SAF2016-79490-R, and PID2019-108489RB-I00) and the Instituto de Salud Carlos III (ISCIII) (AC17/00067, and CB16/11/00405) with cofunding from the European Regional Development Fund (ERDF/FEDER, “Una manera de hacer Europa”), and the Progeria Research Foundation. R.M.N. is supported by the Ministerio de Educación, Cultura y Deporte (pre-doctoral contract FPU16/05027). M.R.H. is supported by the MCIN (post-doctoral contract FJCI-2017-33299). The CNIC is supported by the MCIN, the ISCIII, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titlePremature Vascular Aging with Features of Plaque Vulnerability in an Atheroprone Mouse Model of Hutchinson-Gilford Progeria Syndrome with Ldlr Deficiency.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID33049978es_ES
dc.format.volume9es_ES
dc.format.number10es_ES
dc.identifier.doi10.3390/cells9102252es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderProgeria Research Foundationes_ES
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)es_ES
dc.contributor.funderFundación ProCNICes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2073-4409es_ES
dc.relation.publisherversionhttps://doi.org/10.3390/cells9102252es_ES
dc.identifier.journalCellses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-79490-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PID2019-108489RB-I00es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/AC17/00067es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CB16/11/00405es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU16/05027es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SFJCI-2017-33299es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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