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dc.contributor.authorGonzález-Santamaría, José
dc.contributor.authorVillalba, María
dc.contributor.authorBusnadiego, Oscar
dc.contributor.authorLopez-Olaneta, Marina 
dc.contributor.authorSandoval, Pilar
dc.contributor.authorSnabel, Jessica
dc.contributor.authorLópez-Cabrera, Manuel
dc.contributor.authorErler, Janine T
dc.contributor.authorHanemaaijer, Roeland
dc.contributor.authorLara-Pezzi, Enrique 
dc.contributor.authorRodríguez-Pascual, Fernando
dc.date.accessioned2019-07-29T14:48:47Z
dc.date.available2019-07-29T14:48:47Z
dc.date.issued2016-01
dc.identifier.citationCardiovasc Res. 2016; 109(1):67-78es_ES
dc.identifier.issn0008-6363es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7985
dc.description.abstractAIMS: After myocardial infarction (MI), extensive remodelling of the extracellular matrix contributes to scar formation. While aiming to preserve tissue integrity, this fibrotic response is also associated with adverse events, including a markedly increased risk of heart failure, ventricular arrhythmias, and sudden cardiac death. Cardiac fibrosis is characterized by extensive deposition of collagen and also by increased stiffness as a consequence of enhanced collagen cross-linking. Members of the lysyl oxidase (LOX) family of enzymes are responsible for the formation of collagen cross-links. This study investigates the contribution of LOX family members to the heart response to MI. METHODS AND RESULTS: Experimental MI was induced in C57BL/6 mice by permanent ligation of the left anterior descending coronary artery. The expression of LOX isoforms (LOX and LOXL1-4) was strongly increased upon MI, and this response was accompanied by a significant accumulation of mature collagen fibres in the infarcted area. LOX expression was observed in areas of extensive remodelling, partially overlapping with α-smooth muscle actin-expressing myofibroblasts. Tumour growth factor-β as well as hypoxia-activated pathways contributed to the induction of LOX expression in cardiac fibroblasts. Finally, in vivo post-infarction treatment with the broadband LOX inhibitor β-aminopropionitrile or, selectively, with a neutralizing antibody against the canonical LOX isoform attenuated collagen accumulation and maturation and also resulted in reduced ventricular dilatation and improved cardiac function. CONCLUSION: LOX family members contribute significantly to the detrimental effects of cardiac remodelling, highlighting LOX inhibition as a potential therapeutic strategy for post-infarction recovery.es_ES
dc.description.sponsorshipMinisterio de Economia y Competitividad (Plan Nacional de I+D+I) [SAF2012-34916, SAF2012-31451]; Comunidad Autonoma de Madrid (FIBROTEAM Consortium) [2010-BMD2321]; European Union's FP7 [ERG-239158, CardioNeT-ITN-289600, CardioNext-ITN-608027]; Ministerio de Economia y Competitividad (Formacion de Personal Investigador)es_ES
dc.language.isoenges_ES
dc.publisherEuropean Society of Cardiologyes_ES
dc.relation.isversionofPostprintes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectCardiac fibrosises_ES
dc.subjectCollagenes_ES
dc.subjectLysyl oxidaseses_ES
dc.subjectMyocardial infarctiones_ES
dc.subjectMyofibroblastes_ES
dc.subject.meshAnimals es_ES
dc.subject.meshCell Hypoxia es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshEnzyme Induction es_ES
dc.subject.meshExtracellular Matrix es_ES
dc.subject.meshHeart es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMyocardial Infarction es_ES
dc.subject.meshProtein-Lysine 6-Oxidase es_ES
dc.subject.meshTransforming Growth Factor beta es_ES
dc.titleMatrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunctiones_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID26260798es_ES
dc.format.volume109es_ES
dc.format.number1es_ES
dc.format.page67-78es_ES
dc.identifier.doi10.1093/cvr/cvv214es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderEuropean Commissiones_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1755-3245es_ES
dc.relation.publisherversionhttps://doi.org/10.1093/cvr/cvv214es_ES
dc.identifier.journalCardiovascular researches_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regulación Molecular de la Insuficiencia Cardiacaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/289600/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/608027/EUes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2012-34916es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2012-31451es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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