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dc.contributor.authorMartinez-Martinez, Sara 
dc.contributor.authorLozano-Vidal, Noelia 
dc.contributor.authorLopez-Maderuelo, Dolores 
dc.contributor.authorJimenez-Borreguero, Luis J. 
dc.contributor.authorArmesilla, Ángel Luis
dc.contributor.authorRedondo, Juan Miguel 
dc.date.accessioned2020-04-30T14:40:10Z
dc.date.available2020-04-30T14:40:10Z
dc.date.issued2019-02
dc.identifier.citationFEBS J. 2019; 286(1):46-65es_ES
dc.identifier.issn1742-464Xes_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9850
dc.description.abstractPrevious studies have demonstrated that activation of calcineurin induces pathological cardiac hypertrophy (CH). In these studies, loss-of-function was mostly achieved by systemic administration of the calcineurin inhibitor cyclosporin A. The lack of conditional knockout models for calcineurin function has impeded progress toward defining the role of this protein during the onset and the development of CH in adults. Here, we exploited a mouse model of CH based on the infusion of a hypertensive dose of angiotensin II (AngII) to model the role of calcineurin in CH in adulthood. AngII-induced CH in adult mice was reduced by treatment with cyclosporin A, without affecting the associated increase in blood pressure, and also by induction of calcineurin deletion in adult mouse cardiomyocytes, indicating that cardiomyocyte calcineurin is required for AngII-induced CH. Surprisingly, cardiac-specific deletion of calcineurin, but not treatment of mice with cyclosporin A, significantly reduced AngII-induced cardiac fibrosis and apoptosis. Analysis of profibrotic genes revealed that AngII-induced expression of Tgfβ family members and Lox was not inhibited by cyclosporin A but was markedly reduced by cardiac-specific calcineurin deletion. These results show that AngII induces a direct, calcineurin-dependent prohypertrophic effect in cardiomyocytes, as well as a systemic hypertensive effect that is independent of calcineurin activity.es_ES
dc.description.sponsorshipSpanish Ministerio de Economia, Industria y Competitividad (MEIC); Pro-CNIC Foundation; Severo Ochoa Center of Excellence (MEIC award) [SEV-2015-0505]; MEIC [SAF2012-34296, SAF2015-636333R]; Fundacio La Marato TV3 [CNIC is supported by the Spanish Ministerio de Economia, Industria y Competitividad (MEIC) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505). Support was also provided by grants from MEIC (SAF2012-34296 and SAF2015-636333R to JMR), Fundacio La Marato TV3 (20151330 to JMR), Ministerio de Sanidad CIBERCV (CB16/11/00264 to JMR), Comunidad de Madrid (AORTASANA-CM; B2017/BMD-3676 to JMR), and Red de Investigacion Cardiovascular (RIC) (RD12/0042/0022 to JMR and RD12/0042/0056 to LJJ-B), and an FPU fellowship (AP 2009-1713 to NL-V). We thank Dr S. Bartlett for English language editing, Dr Fatima Sanchez Cabo for statistical advice, Dr M. R. Campanero, Dr J. F. Nistal, and Dr B. Ibanez for critical reading of the manuscript. We also thank Dr G. R. Crabtree for providing Cnb1<SUP>Delta/flox</SUP> mice, A. Peral for technical assistance, and the ultrasonographers A.V. Alonso and L. Flores for technical support.]; Ministerio de Sanidad CIBERCV [CB16/11/00264]; Comunidad de Madrid (AORTASANA-CM) [B2017/BMD-3676]; Red de Investigacion Cardiovascular (RIC) [RD12/0042/0022, RD12/0042/0056]; FPU fellowship [AP 2009-1713]es_ES
dc.language.isoenges_ES
dc.publisherFederation of European Biochemical Societieses_ES
dc.relation.isversionofPostprintes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectangiotensin IIes_ES
dc.subjectcyclosporin Aes_ES
dc.subjectheartes_ES
dc.subjectpro-fibrotic geneses_ES
dc.subject.meshAngiotensin II es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshCalcineurin es_ES
dc.subject.meshCardiomegaly es_ES
dc.subject.meshDisease Progression es_ES
dc.subject.meshFibrosis es_ES
dc.subject.meshGene Expression Profiling es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshMyocytes, Cardiaces_ES
dc.subject.meshSignal Transduction es_ES
dc.subject.meshVasoconstrictor Agents es_ES
dc.titleCardiomyocyte calcineurin is required for the onset and progression of cardiac hypertrophy and fibrosis in adult micees_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID30548183es_ES
dc.format.volume286es_ES
dc.format.number1es_ES
dc.format.page46-65es_ES
dc.identifier.doi10.1111/febs.14718es_ES
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)es_ES
dc.contributor.funderFundación ProCNICes_ES
dc.contributor.funderFundació La Maratóes_ES
dc.contributor.funderMinisterio de Sanidad y Consumo (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1742-4658es_ES
dc.relation.publisherversionhttps://doi.org/10.1111/febs.14718es_ES
dc.identifier.journalThe FEBS journales_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamaciónes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2012-34296es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-636333Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CB16/11/00264es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0042/0022es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0042/0056es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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