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dc.contributor.authorZak, Magdalena M. 
dc.contributor.authorGkontra, Polyxeni 
dc.contributor.authorClemente, Cristina 
dc.contributor.authorSquadrito, Mario Leonardo
dc.contributor.authorFerrarini, Alessia 
dc.contributor.authorMota, Ruben A. 
dc.contributor.authorOliver, Eduardo 
dc.contributor.authorRocha, Susana 
dc.contributor.authorAguero, Jaume 
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorDe Palma, Michele
dc.contributor.authorIbanez, Borja 
dc.contributor.authorArroyo, Alicia G
dc.identifier.citationHum Gene Ther. 2019; 30(7):839-905es_ES
dc.description.abstractMicrovascular dysfunction and resulting tissue hypoxia is a major contributor to the pathogenesis and evolution of cardiovascular diseases (CVD). Diverse gene and cell therapies have been proposed to preserve the microvasculature or boost angiogenesis in CVD, with moderate benefit. This study tested in vivo the impact of sequential delivery by bone-marrow (BM) cells of the pro-angiogenic factors vascular endothelial growth factor (VEGFA) and sphingosine-1-phosphate (S1P) in a myocardial infarction model. For that, mouse BM cells were transduced with lentiviral vectors coding for VEGFA or sphingosine kinase (SPHK1), which catalyzes S1P production, and injected them intravenously 4 and 7 days after cardiac ischemia-reperfusion in mice. Sequential delivery by transduced BM cells of VEGFA and S1P led to increased endothelial cell numbers and shorter extravascular distances in the infarct zone, which support better oxygen diffusion 28 days post myocardial infarction, as shown by automated 3D image analysis of the microvasculature. Milder effects were observed in the remote zone, together with increased proportion of capillaries. BM cells delivering VEGFA and S1P also decreased myofibroblast abundance and restricted adverse cardiac remodeling without major impact on cardiac contractility. The results indicate that BM cells engineered to deliver VEGFA/S1P angiogenic factors sequentially may constitute a promising strategy to improve micro-vascularization and oxygen diffusion, thus limiting the adverse consequences of cardiac ischemia.es_ES
dc.description.sponsorshipThis study was supported by grants from the Spanish Ministerio de Ciencia, Innovacion y Universidades SAF2014-52050-R and SAF2017-83229-R to A.G.A. and BIO2015-67580-P to J.V. and the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (PRB2, IPT13/0001-ISCIII-SGEFI/FEDER, ProteoRed). The research leading to these results received funding from the People Programme (Marie Curie Action) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant Agreement 608027. The CNIC is supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (award SEV-2015-0505).es_ES
dc.publisherMary Ann Liebertes_ES
dc.subjectcardiac remodelinges_ES
dc.subjectgene–cell angiotherapyes_ES
dc.subjectmyocardial infarctiones_ES
dc.subjectoxygen diffusiones_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBiomarkers es_ES
dc.subject.meshBone Marrow Cells es_ES
dc.subject.meshCell- and Tissue-Based Therapy es_ES
dc.subject.meshDisease Models, Animales_ES
dc.subject.meshGenetic Therapy es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLysophospholipids es_ES
dc.subject.meshMice es_ES
dc.subject.meshMyocardial Infarction es_ES
dc.subject.meshNeovascularization, Pathologices_ES
dc.subject.meshSphingosine es_ES
dc.subject.meshVascular Endothelial Growth Factor A es_ES
dc.subject.meshVentricular Remodeling es_ES
dc.titleSequential Bone-Marrow Cell Delivery of VEGFA/S1P Improves Vascularization and Limits Adverse Cardiac Remodeling After Myocardial Infarction in Micees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Commissiones_ES
dc.contributor.funderFundación ProCNICes_ES
dc.identifier.journalHuman gene therapyes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Metaloproteinasas de Matriz en Angiogénesis e Inflamaciónes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Laboratorio Traslacional para la Imagen y Terapia Cardiovasculares_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovasculares_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Proteómica / Metabolómicaes_ES

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional