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dc.contributor.author | Clemente-Moragón, Agustín | |
dc.contributor.author | Gomez, Monica | |
dc.contributor.author | Villena-Gutierrez, Rocio | |
dc.contributor.author | Lalama, Doménica V | |
dc.contributor.author | Garcia-Prieto, Jaime | |
dc.contributor.author | Martinez, Fernando | |
dc.contributor.author | Sanchez-Cabo, Fatima | |
dc.contributor.author | Fuster, Valentin | |
dc.contributor.author | Oliver, Eduardo | |
dc.contributor.author | Ibáñez, Borja | |
dc.date.accessioned | 2021-04-07T09:54:46Z | |
dc.date.available | 2021-04-07T09:54:46Z | |
dc.date.issued | 2020-12 | |
dc.identifier.citation | Eur Heart J. 2020; 41(46):4425-4440 | es_ES |
dc.identifier.issn | 1522-9645 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/12542 | |
dc.description.abstract | Clinical 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.sponsorship | Ministry 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.iso | eng | es_ES |
dc.publisher | Oxford University Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | * |
dc.title | Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial 4.0 Internacional | * |
dc.identifier.pubmedID | 33026079 | es_ES |
dc.format.volume | 41 | es_ES |
dc.format.number | 46 | es_ES |
dc.format.page | 4425-4440 | es_ES |
dc.identifier.doi | 10.1093/eurheartj/ehaa733 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | https://doi.org/10.1093/eurheartj/ehaa733 | es_ES |
dc.identifier.journal | European heart journal | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovascular | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Investigación Cardiovascular Traslacional Multidisciplinaria | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Bioinformática | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PID2019-107332RB-I00 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI16/02110), | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/S2017/BMD-3867 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/2017-T1/BMD-5185 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/FPU2017/01932 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PFIS FI17/00045 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PEJ-2017-TL/BMD-6463 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/AC16/00021 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/819775 | es_ES |
dc.rights.accessRights | open access | es_ES |