dc.contributor.author | Zak, Magdalena M. | |
dc.contributor.author | Gkontra, Polyxeni | |
dc.contributor.author | Clemente, Cristina | |
dc.contributor.author | Squadrito, Mario Leonardo | |
dc.contributor.author | Ferrarini, Alessia | |
dc.contributor.author | Mota, Ruben A. | |
dc.contributor.author | Oliver, Eduardo | |
dc.contributor.author | Rocha, Susana | |
dc.contributor.author | Aguero, Jaume | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | De Palma, Michele | |
dc.contributor.author | Ibáñez, Borja | |
dc.contributor.author | Arroyo, Alicia G | |
dc.date.accessioned | 2020-05-08T09:37:08Z | |
dc.date.available | 2020-05-08T09:37:08Z | |
dc.date.issued | 2019-07 | |
dc.identifier.citation | Hum Gene Ther. 2019; 30(7):839-905 | es_ES |
dc.identifier.issn | 1043-0342 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9981 | |
dc.description.abstract | Microvascular 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.sponsorship | This 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.language.iso | eng | es_ES |
dc.publisher | Mary Ann Liebert | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | S1P | es_ES |
dc.subject | VEGFA | es_ES |
dc.subject | Cardiac remodeling | es_ES |
dc.subject | Gene-cell angiotherapy | es_ES |
dc.subject | Myocardial infarction | es_ES |
dc.subject | Oxygen diffusion | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Biomarkers | es_ES |
dc.subject.mesh | Bone Marrow Cells | es_ES |
dc.subject.mesh | Cell- and Tissue-Based Therapy | es_ES |
dc.subject.mesh | Disease Models, Animal | es_ES |
dc.subject.mesh | Genetic Therapy | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Lysophospholipids | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Myocardial Infarction | es_ES |
dc.subject.mesh | Neovascularization, Pathologic | es_ES |
dc.subject.mesh | Sphingosine | es_ES |
dc.subject.mesh | Vascular Endothelial Growth Factor A | es_ES |
dc.subject.mesh | Ventricular Remodeling | es_ES |
dc.title | Sequential Bone-Marrow Cell Delivery of VEGFA/S1P Improves Vascularization and Limits Adverse Cardiac Remodeling After Myocardial Infarction in Mice | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 30786776 | es_ES |
dc.format.volume | 30 | es_ES |
dc.format.number | 7 | es_ES |
dc.format.page | 893-905 | es_ES |
dc.identifier.doi | 10.1089/hum.2018.194 | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | es_ES |
dc.embargo.terms | 2020-07-01 | es_ES |
dc.identifier.e-issn | 1557-7422 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1089/hum.2018.194 | es_ES |
dc.identifier.journal | Human gene therapy | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Metaloproteinasas de Matriz en Angiogénesis e Inflamación | 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::Proteómica cardiovascular | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2014-52050-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2017-83229-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/BIO2015-67580-P | es_ES |
dc.rights.accessRights | open access | es_ES |