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dc.contributor.authorVillahoz, Silvia 
dc.contributor.authorYunes-Leites, Paula Sofía 
dc.contributor.authorMendez-Barbero, Nerea 
dc.contributor.authorUrso, Katia 
dc.contributor.authorBonzon-Kulichenko, Elena 
dc.contributor.authorOrtega Jimenez, Sagrario 
dc.contributor.authorNistal, J Francisco
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorOffermanns, Stefan
dc.contributor.authorRedondo, Juan Miguel 
dc.contributor.authorCampanero, Miguel R
dc.date.accessioned2018-11-29T10:07:57Z
dc.date.available2018-11-29T10:07:57Z
dc.date.issued2018-11-15
dc.identifier.citationNat Commun. 2018; 9(1): 4795.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6739
dc.description.abstractAortic intramural hematoma (IMH) can evolve toward reabsorption, dissection or aneurysm. Hypertension is the most common predisposing factor in IMH and aneurysm patients, and the hypertensive mediator angiotensin-II induces both in mice. We have previously shown that constitutive deletion of Rcan1 isoforms prevents Angiotensin II-induced aneurysm in mice. Here we generate mice conditionally lacking each isoform or all isoforms in vascular smooth muscle cells, endothelial cells, or ubiquitously, to determine the contribution to aneurysm development of Rcan1 isoforms in vascular cells. Surprisingly, conditional Rcan1 deletion in either vascular cell-type induces a hypercontractile phenotype and aortic medial layer disorganization, predisposing to hypertension-mediated aortic rupture, IMH, and aneurysm. These processes are blocked by ROCK inhibition. We find that Rcan1 associates with GSK-3β, whose inhibition decreases myosin activation. Our results identify potential therapeutic targets for intervention in IMH and aneurysm and call for caution when interpreting phenotypes of constitutively and inducibly deficient mice.es_ES
dc.description.sponsorshipWe thank Dr. Ralf H. Adams (Max Planck Institute, Münster, Germany), Dr. Marcos Malumbres (CNIO, Madrid, Spain), Dr. Miguel Torres (CNIC, Madrid, Spain), and Dr. Alicia G. Arroyo (CNIC) for supplying the Cdh5-CreERT2, Ubc-CreERT2, Rosa26-LSLYFP, and Rosa26-LSL-Tomato mice, respectively. We further thank Dr. Javier Regadera (Universidad Autónoma de Madrid, Spain) and Dr. Gustavo Egea (Universitat de Barcelona, Spain) for advice on histological studies, S. Bartlett for English language editing, and the CNIC histology facility, and Beatriz C. Ornés for technical support. CNIC is supported by the Spanish Ministerio de Ciencia, Investigación y Universidades (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Support was also provided by grants from MINECO (grants SAF2013-45258P and SAF2017-88881R (M.R.C.), SAF2015-636333R (J.M.R.), PI15/01224 (J.F.N.), and BIO2015-67580-P (J.V.)), Comunidad de Madrid (grant AORTASANA-CM; B2017/BMD-3676 (M.R.C. and J.M.R.)), CSIC (M.R.C.), fundacion La Marato TV3 (grant 20151330 (J.M.R.)), The Marfan Foundation Faculty grant 2017 (J.M.R.), and the CIBERCV of Ministerio de Sanidad (grants CB16/11/00264 (J.M.R.) and CB16/11/00277 (J.V.)). S.V. and P.S.Y.-L. hold FPI fellowships SVP-2013-067777 and BES-2016-076637, respectively. The cost of this publication was paid in part with FEDER funds.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectSYNDROME CRITICAL REGIONes_ES
dc.subjectCALCINEURIN INHIBITOR DSCR1es_ES
dc.subjectVASCULAR SMOOTH-MUSCLEes_ES
dc.subjectPEPTIDE IDENTIFICATIONes_ES
dc.subjectSTRIATED-MUSCLESes_ES
dc.subjectOXIDATIVE STRESSes_ES
dc.subjectCELL-MIGRATIONes_ES
dc.subjectTUMOR-GROWTHes_ES
dc.subject1 GENEes_ES
dc.subjectMICEes_ES
dc.titleConditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupturees_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30442942es_ES
dc.format.volume9es_ES
dc.format.number1es_ES
dc.format.page4795es_ES
dc.identifier.doi10.1038/s41467-018-07071-7es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderFundación La Mataró TV3es_ES
dc.contributor.funderMarfan Foundationes_ES
dc.contributor.funderMinisterio de Sanidad y Consumo (España)es_ES
dc.contributor.funderFundación ProCNICes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-018-07071-7.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamación
dc.repisalud.institucionCNIOes_ES
dc.repisalud.institucionCNIC
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Ratones Transgénicoses_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013-45258Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2017-88881Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-636333Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI15/01224es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BIO2015-67580-Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CB16/11/00264es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CB16/11/00277es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SVP-2013-067777es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2016-076637es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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