Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction

Autores
Olea, Fernanda Daniela; De Lorenzi, Andrea; Cortés, Claudia; Cuniberti, Luis Alberto; Fazzi, Lucía; Flamenco, María del Pilar; Locatelli, Paola; Cabeza Meckert, Patricia; Bercovich, Andrés; Laguens, Rubén; Crottogini, Alberto José
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: In reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI. METHODS: Adult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus intravenous EPO 1000 IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8). RESULTS: Fifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8 ± 1 %; pVEGF: 16 ± 5 %; EPO: 13 ± 4 %) compared to placebo (25 ± 7 %, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect. CONCLUSIONS: Combined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.
Fil: Olea, Fernanda Daniela. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: De Lorenzi, Andrea. Fundación Favaloro; Argentina
Fil: Cortés, Claudia. Fundación Favaloro; Argentina
Fil: Cuniberti, Luis Alberto. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fazzi, Lucía. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Flamenco, María del Pilar. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina
Fil: Locatelli, Paola. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabeza Meckert, Patricia. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina
Fil: Bercovich, Andrés. Bio Sidus; Argentina
Fil: Laguens, Rubén. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Crottogini, Alberto José. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Vegf
Erythropoietin
Reperfused Myocardial Infarction
Apoptosis
Sheep
Gene Therapy
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24169
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/24169
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarctionOlea, Fernanda DanielaDe Lorenzi, AndreaCortés, ClaudiaCuniberti, Luis AlbertoFazzi, LucíaFlamenco, María del PilarLocatelli, PaolaCabeza Meckert, PatriciaBercovich, AndrésLaguens, RubénCrottogini, Alberto JoséVegfErythropoietinReperfused Myocardial InfarctionApoptosisSheepGene Therapyhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BACKGROUND: In reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI. METHODS: Adult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus intravenous EPO 1000 IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8). RESULTS: Fifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8 ± 1 %; pVEGF: 16 ± 5 %; EPO: 13 ± 4 %) compared to placebo (25 ± 7 %, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect. CONCLUSIONS: Combined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.Fil: Olea, Fernanda Daniela. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: De Lorenzi, Andrea. Fundación Favaloro; ArgentinaFil: Cortés, Claudia. Fundación Favaloro; ArgentinaFil: Cuniberti, Luis Alberto. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fazzi, Lucía. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flamenco, María del Pilar. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Locatelli, Paola. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabeza Meckert, Patricia. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; ArgentinaFil: Bercovich, Andrés. Bio Sidus; ArgentinaFil: Laguens, Rubén. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Crottogini, Alberto José. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Ireland2013-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24169Olea, Fernanda Daniela; De Lorenzi, Andrea; Cortés, Claudia; Cuniberti, Luis Alberto; Fazzi, Lucía; et al.; Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction; Elsevier Ireland; International Journal of Cardiology; 165; 2; 5-2013; 291-2980167-5273CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0167527311009193info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijcard.2011.08.078info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:37:32Zoai:ri.conicet.gov.ar:11336/24169instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:37:32.295CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction
title Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction
spellingShingle Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction
Olea, Fernanda Daniela
Vegf
Erythropoietin
Reperfused Myocardial Infarction
Apoptosis
Sheep
Gene Therapy
title_short Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction
title_full Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction
title_fullStr Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction
title_full_unstemmed Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction
title_sort Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction
dc.creator.none.fl_str_mv Olea, Fernanda Daniela
De Lorenzi, Andrea
Cortés, Claudia
Cuniberti, Luis Alberto
Fazzi, Lucía
Flamenco, María del Pilar
Locatelli, Paola
Cabeza Meckert, Patricia
Bercovich, Andrés
Laguens, Rubén
Crottogini, Alberto José
author Olea, Fernanda Daniela
author_facet Olea, Fernanda Daniela
De Lorenzi, Andrea
Cortés, Claudia
Cuniberti, Luis Alberto
Fazzi, Lucía
Flamenco, María del Pilar
Locatelli, Paola
Cabeza Meckert, Patricia
Bercovich, Andrés
Laguens, Rubén
Crottogini, Alberto José
author_role author
author2 De Lorenzi, Andrea
Cortés, Claudia
Cuniberti, Luis Alberto
Fazzi, Lucía
Flamenco, María del Pilar
Locatelli, Paola
Cabeza Meckert, Patricia
Bercovich, Andrés
Laguens, Rubén
Crottogini, Alberto José
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Vegf
Erythropoietin
Reperfused Myocardial Infarction
Apoptosis
Sheep
Gene Therapy
topic Vegf
Erythropoietin
Reperfused Myocardial Infarction
Apoptosis
Sheep
Gene Therapy
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: In reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI. METHODS: Adult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus intravenous EPO 1000 IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8). RESULTS: Fifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8 ± 1 %; pVEGF: 16 ± 5 %; EPO: 13 ± 4 %) compared to placebo (25 ± 7 %, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect. CONCLUSIONS: Combined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.
Fil: Olea, Fernanda Daniela. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: De Lorenzi, Andrea. Fundación Favaloro; Argentina
Fil: Cortés, Claudia. Fundación Favaloro; Argentina
Fil: Cuniberti, Luis Alberto. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fazzi, Lucía. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Flamenco, María del Pilar. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina
Fil: Locatelli, Paola. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabeza Meckert, Patricia. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina
Fil: Bercovich, Andrés. Bio Sidus; Argentina
Fil: Laguens, Rubén. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Básicas de la Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Crottogini, Alberto José. Universidad Favaloro. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description BACKGROUND: In reperfused acute myocardial infarction (RAMI), cardioprotective treatments may enhance myocardial salvage and hence reduce the area of necrosis. Based on studies showing that plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer reduces infarct size by combining angio-arteriogenic and cardiomyogenic effects and that erythropoietin (EPO) exerts anti-apoptotic actions in animal models of AMI, we aimed to assess if their association would reduce infarct size to a larger extent than any of them individually in a large mammalian model of RAMI. METHODS: Adult sheep subjected to 90-minute coronary artery occlusion received upon reperfusion intramyocardial pVEGF 3.8 mg plus intravenous EPO 1000 IU/kg (n=8), pVEGF (n=8), EPO (n=8) or placebo (n=8). RESULTS: Fifteen days after treatment, infarct size was smaller in the 3 treatment groups (pVEGF+EPO: 8 ± 1 %; pVEGF: 16 ± 5 %; EPO: 13 ± 4 %) compared to placebo (25 ± 7 %, p<0.001). However, in the EPO+VEGF group infarct size was significantly smaller than in the groups receiving EPO or VEGF individually (p<0.05). DNA fragmentation, a hallmark of late apoptosis, was significantly lower in sheep receiving EPO. The combined treatment, while not affecting global left ventricular performance, improved regional peri-infarct function and prevented over-time expansion of the post-infarct perfusion defect. CONCLUSIONS: Combined pVEGF and EPO treatment might be clinically useful to enhance the benefits of early revascularization in patients with acute myocardial infarction.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/24169
Olea, Fernanda Daniela; De Lorenzi, Andrea; Cortés, Claudia; Cuniberti, Luis Alberto; Fazzi, Lucía; et al.; Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction; Elsevier Ireland; International Journal of Cardiology; 165; 2; 5-2013; 291-298
0167-5273
CONICET Digital
CONICET
url http://hdl.handle.net/11336/24169
identifier_str_mv Olea, Fernanda Daniela; De Lorenzi, Andrea; Cortés, Claudia; Cuniberti, Luis Alberto; Fazzi, Lucía; et al.; Combined VEGF gene transfer and erythropoietin in ovine reperfused myocardial infarction; Elsevier Ireland; International Journal of Cardiology; 165; 2; 5-2013; 291-298
0167-5273
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0167527311009193
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijcard.2011.08.078
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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