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dc.contributor.authorClemente-Moragón, Agustín
dc.contributor.authorGomez, Monica 
dc.contributor.authorVillena-Gutierrez, Rocio 
dc.contributor.authorLalama, Doménica V
dc.contributor.authorGarcia-Prieto, Jaime 
dc.contributor.authorMartinez, Fernando 
dc.contributor.authorSanchez-Cabo, Fatima 
dc.contributor.authorFuster, Valentin 
dc.contributor.authorOliver, Eduardo 
dc.contributor.authorIbanez, Borja 
dc.date.accessioned2021-04-07T09:54:46Z
dc.date.available2021-04-07T09:54:46Z
dc.date.issued2020-12
dc.identifier.citationEur Heart J. 2020; 41(46):4425-4440es_ES
dc.identifier.issn1522-9645
dc.identifier.urihttp://hdl.handle.net/20.500.12105/12542
dc.description.abstractClinical guidelines recommend early intravenous β-blockers during ongoing myocardial infarction; however, it is unknown whether all β-blockers exert a similar cardioprotective effect. We experimentally compared three clinically approved intravenous β-blockers. Mice undergoing 45 min/24 h ischaemia-reperfusion (I/R) received vehicle, metoprolol, atenolol, or propranolol at min 35. The effect on neutrophil infiltration was tested in three models of exacerbated inflammation. Neutrophil migration was evaluated in vitro and in vivo by intravital microscopy. The effect of β-blockers on the conformation of the β1 adrenergic receptor was studied in silico. Of the tested β-blockers, only metoprolol ameliorated I/R injury [infarct size (IS) = 18.0% ± 0.03% for metoprolol vs. 35.9% ± 0.03% for vehicle; P < 0.01]. Atenolol and propranolol had no effect on IS. In the three exacerbated inflammation models, neutrophil infiltration was significantly attenuated only in the presence of metoprolol (60%, 50%, and 70% reductions vs. vehicle in myocardial I/R injury, thioglycolate-induced peritonitis, and lipopolysaccharide-induced acute lung injury, respectively). Migration studies confirmed the particular ability of metoprolol to disrupt neutrophil dynamics. In silico analysis indicated different intracellular β1 adrenergic receptor conformational changes when bound to metoprolol than to the other two β-blockers. Metoprolol exerts a disruptive action on neutrophil dynamics during exacerbated inflammation, resulting in an infarct-limiting effect not observed with atenolol or propranolol. The differential effect of β-blockers may be related to distinct conformational changes in the β1 adrenergic receptor upon metoprolol binding. If these data are confirmed in a clinical trial, metoprolol should become the intravenous β-blocker of choice for patients with ongoing infarction.es_ES
dc.description.sponsorshipMinistry of Science and Innovation (‘RETOS 2019’ grant N_ PID2019-107332RB-I00), Instituto de Salud Carlos III (ISCIII; PI16/02110), and European Regional Development Fund (# AC16/00021), Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). B.I. is supported by an ERCCoG grant (819775). E.O. is supported by funds from the Comunidad de Madrid Programa de Atraccion de Talento (2017-T1/BMD-5185). A.C-M. and R.V-G are supported by fellowships from the Ministerio de Ciencia e Innovacion (MCN) and ISCIII (FPU2017/01932 and PFIS FI17/00045). D.V.L. is supported by an Iniciativa de Empleo Juvenil grant (PEJ-2017-TL/BMD-6463) from the Comunidad de Madrid. The CNIC is supported by the ISCIII, the MCN, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).es_ES
dc.language.isoenges_ES
dc.publisherOxford University Presses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.titleMetoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial 4.0 Internacional*
dc.identifier.pubmedID33026079es_ES
dc.format.volume41es_ES
dc.format.number46es_ES
dc.format.page4425-4440es_ES
dc.identifier.doi10.1093/eurheartj/ehaa733es_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.funderComunidad de Madrides_ES
dc.contributor.funderFundación ProCNICes_ES
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1093/eurheartj/ehaa733es_ES
dc.identifier.journalEuropean heart journales_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovasculares_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Investigación Cardiovascular Traslacional Multidisciplinariaes_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Bioinformáticaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PID2019-107332RB-I00es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI16/02110),es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/S2017/BMD-3867es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/2017-T1/BMD-5185es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU2017/01932es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PFIS FI17/00045es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PEJ-2017-TL/BMD-6463es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/AC16/00021es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/819775es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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