Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion

Autores
Vera Janavel, Gustavo L.; De Lorenzi, Andrea; Cortés, Claudia; Olea, Fernanda Daniela; Cabeza Meckert, Patricia; Bercovich, Andrés; Criscuolo, Marcelo; Laguens, Rubén; Crottogini, Alberto Jose
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: In large mammalian models of acute myocardial infarction (AMI), plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer has been shown to induce angio-arteriogenesis, proliferation of myocyte precursors and adult cardiomyocyte mitosis, reducing infarct size at 15days after coronary artery occlusion. However, it is unknown whether these effects persist at longer follow-up times, nor how they affect cardiac performance. We thus assessed infarct size, left ventricular (LV) function and perfusion in 2-month-old ovine AMI. Methods: Adult sheep with coronary artery occlusion were randomized to blindly receive ten intramyocardial injections of 3.8mg of pVEGF or empty plasmid distributed at the infarct border. Three and 60days later, LV perfusion (single-photon emission computed tomography) and function (stress echocardiography) were assessed. Finally, hemodynamics (LV catheterization), scar size and peri-infarct histology were studied. Results: Infarct size was 30% smaller in pVEGF-treated sheep (23.6±1.9% versus 32.7±2.7% of the LV; p<0.02). Percentage fractional shortening and wall thickening at the infarct border improved after pVEGF, as did myocardial perfusion and LV wall motion under pharmacological stress. Global LV function did not differ between groups, although the force-frequency response was preserved in pVEGF group and lost in placebo animals. These effects were associated with angio-arteriogenesis and proliferation of cardiomyocyte precursors. Conclusions: In sheep with AMI, pVEGF gene transfer affords long-term infarct size reduction, yielding regional LV function and perfusion improvement and reducing remodeling progression. These results suggest the potential usefulness of this approach in the clinical setting.
Fil: Vera Janavel, Gustavo L.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: De Lorenzi, Andrea. Fundación Favaloro; Argentina
Fil: Cortés, Claudia. Fundación Favaloro; Argentina
Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabeza Meckert, Patricia. Fundación Favaloro; Argentina
Fil: Bercovich, Andrés. Biosidus S. A.; Argentina
Fil: Criscuolo, Marcelo. Biosidus S. A.; Argentina
Fil: Laguens, Rubén. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Crottogini, Alberto Jose. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
ANGIOGENESIS
GENE THERAPY
MYOCARDIAL INFARCTION
REMODELING
SHEEP
VEGF
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:11336/192882
Acceder
id CONICETDig_9e247443b4b0a46f735a29bebef28586
oai_identifier_str oai:ri.conicet.gov.ar:11336/192882
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusionVera Janavel, Gustavo L.De Lorenzi, AndreaCortés, ClaudiaOlea, Fernanda DanielaCabeza Meckert, PatriciaBercovich, AndrésCriscuolo, MarceloLaguens, RubénCrottogini, Alberto JoseANGIOGENESISGENE THERAPYMYOCARDIAL INFARCTIONREMODELINGSHEEPVEGFhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Background: In large mammalian models of acute myocardial infarction (AMI), plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer has been shown to induce angio-arteriogenesis, proliferation of myocyte precursors and adult cardiomyocyte mitosis, reducing infarct size at 15days after coronary artery occlusion. However, it is unknown whether these effects persist at longer follow-up times, nor how they affect cardiac performance. We thus assessed infarct size, left ventricular (LV) function and perfusion in 2-month-old ovine AMI. Methods: Adult sheep with coronary artery occlusion were randomized to blindly receive ten intramyocardial injections of 3.8mg of pVEGF or empty plasmid distributed at the infarct border. Three and 60days later, LV perfusion (single-photon emission computed tomography) and function (stress echocardiography) were assessed. Finally, hemodynamics (LV catheterization), scar size and peri-infarct histology were studied. Results: Infarct size was 30% smaller in pVEGF-treated sheep (23.6±1.9% versus 32.7±2.7% of the LV; p<0.02). Percentage fractional shortening and wall thickening at the infarct border improved after pVEGF, as did myocardial perfusion and LV wall motion under pharmacological stress. Global LV function did not differ between groups, although the force-frequency response was preserved in pVEGF group and lost in placebo animals. These effects were associated with angio-arteriogenesis and proliferation of cardiomyocyte precursors. Conclusions: In sheep with AMI, pVEGF gene transfer affords long-term infarct size reduction, yielding regional LV function and perfusion improvement and reducing remodeling progression. These results suggest the potential usefulness of this approach in the clinical setting.Fil: Vera Janavel, Gustavo L.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: De Lorenzi, Andrea. Fundación Favaloro; ArgentinaFil: Cortés, Claudia. Fundación Favaloro; ArgentinaFil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabeza Meckert, Patricia. Fundación Favaloro; ArgentinaFil: Bercovich, Andrés. Biosidus S. A.; ArgentinaFil: Criscuolo, Marcelo. Biosidus S. A.; ArgentinaFil: Laguens, Rubén. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Crottogini, Alberto Jose. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaJohn Wiley & Sons Ltd2012-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/192882Vera Janavel, Gustavo L.; De Lorenzi, Andrea; Cortés, Claudia; Olea, Fernanda Daniela; Cabeza Meckert, Patricia; et al.; Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion; John Wiley & Sons Ltd; Journal Of Gene Medicine; 14; 4; 4-2012; 279-2871099-498XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/jgm.1608info:eu-repo/semantics/altIdentifier/doi/10.1002/jgm.1608info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:02:20Zoai:ri.conicet.gov.ar:11336/192882instacron: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:34982025-10-22 11:02:20.712CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion
title Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion
spellingShingle Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion
Vera Janavel, Gustavo L.
ANGIOGENESIS
GENE THERAPY
MYOCARDIAL INFARCTION
REMODELING
SHEEP
VEGF
title_short Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion
title_full Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion
title_fullStr Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion
title_full_unstemmed Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion
title_sort Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion
dc.creator.none.fl_str_mv Vera Janavel, Gustavo L.
De Lorenzi, Andrea
Cortés, Claudia
Olea, Fernanda Daniela
Cabeza Meckert, Patricia
Bercovich, Andrés
Criscuolo, Marcelo
Laguens, Rubén
Crottogini, Alberto Jose
author Vera Janavel, Gustavo L.
author_facet Vera Janavel, Gustavo L.
De Lorenzi, Andrea
Cortés, Claudia
Olea, Fernanda Daniela
Cabeza Meckert, Patricia
Bercovich, Andrés
Criscuolo, Marcelo
Laguens, Rubén
Crottogini, Alberto Jose
author_role author
author2 De Lorenzi, Andrea
Cortés, Claudia
Olea, Fernanda Daniela
Cabeza Meckert, Patricia
Bercovich, Andrés
Criscuolo, Marcelo
Laguens, Rubén
Crottogini, Alberto Jose
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOGENESIS
GENE THERAPY
MYOCARDIAL INFARCTION
REMODELING
SHEEP
VEGF
topic ANGIOGENESIS
GENE THERAPY
MYOCARDIAL INFARCTION
REMODELING
SHEEP
VEGF
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: In large mammalian models of acute myocardial infarction (AMI), plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer has been shown to induce angio-arteriogenesis, proliferation of myocyte precursors and adult cardiomyocyte mitosis, reducing infarct size at 15days after coronary artery occlusion. However, it is unknown whether these effects persist at longer follow-up times, nor how they affect cardiac performance. We thus assessed infarct size, left ventricular (LV) function and perfusion in 2-month-old ovine AMI. Methods: Adult sheep with coronary artery occlusion were randomized to blindly receive ten intramyocardial injections of 3.8mg of pVEGF or empty plasmid distributed at the infarct border. Three and 60days later, LV perfusion (single-photon emission computed tomography) and function (stress echocardiography) were assessed. Finally, hemodynamics (LV catheterization), scar size and peri-infarct histology were studied. Results: Infarct size was 30% smaller in pVEGF-treated sheep (23.6±1.9% versus 32.7±2.7% of the LV; p<0.02). Percentage fractional shortening and wall thickening at the infarct border improved after pVEGF, as did myocardial perfusion and LV wall motion under pharmacological stress. Global LV function did not differ between groups, although the force-frequency response was preserved in pVEGF group and lost in placebo animals. These effects were associated with angio-arteriogenesis and proliferation of cardiomyocyte precursors. Conclusions: In sheep with AMI, pVEGF gene transfer affords long-term infarct size reduction, yielding regional LV function and perfusion improvement and reducing remodeling progression. These results suggest the potential usefulness of this approach in the clinical setting.
Fil: Vera Janavel, Gustavo L.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: De Lorenzi, Andrea. Fundación Favaloro; Argentina
Fil: Cortés, Claudia. Fundación Favaloro; Argentina
Fil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabeza Meckert, Patricia. Fundación Favaloro; Argentina
Fil: Bercovich, Andrés. Biosidus S. A.; Argentina
Fil: Criscuolo, Marcelo. Biosidus S. A.; Argentina
Fil: Laguens, Rubén. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
Fil: Crottogini, Alberto Jose. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background: In large mammalian models of acute myocardial infarction (AMI), plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer has been shown to induce angio-arteriogenesis, proliferation of myocyte precursors and adult cardiomyocyte mitosis, reducing infarct size at 15days after coronary artery occlusion. However, it is unknown whether these effects persist at longer follow-up times, nor how they affect cardiac performance. We thus assessed infarct size, left ventricular (LV) function and perfusion in 2-month-old ovine AMI. Methods: Adult sheep with coronary artery occlusion were randomized to blindly receive ten intramyocardial injections of 3.8mg of pVEGF or empty plasmid distributed at the infarct border. Three and 60days later, LV perfusion (single-photon emission computed tomography) and function (stress echocardiography) were assessed. Finally, hemodynamics (LV catheterization), scar size and peri-infarct histology were studied. Results: Infarct size was 30% smaller in pVEGF-treated sheep (23.6±1.9% versus 32.7±2.7% of the LV; p<0.02). Percentage fractional shortening and wall thickening at the infarct border improved after pVEGF, as did myocardial perfusion and LV wall motion under pharmacological stress. Global LV function did not differ between groups, although the force-frequency response was preserved in pVEGF group and lost in placebo animals. These effects were associated with angio-arteriogenesis and proliferation of cardiomyocyte precursors. Conclusions: In sheep with AMI, pVEGF gene transfer affords long-term infarct size reduction, yielding regional LV function and perfusion improvement and reducing remodeling progression. These results suggest the potential usefulness of this approach in the clinical setting.
publishDate 2012
dc.date.none.fl_str_mv 2012-04
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/11336/192882
Vera Janavel, Gustavo L.; De Lorenzi, Andrea; Cortés, Claudia; Olea, Fernanda Daniela; Cabeza Meckert, Patricia; et al.; Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion; John Wiley & Sons Ltd; Journal Of Gene Medicine; 14; 4; 4-2012; 279-287
1099-498X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/192882
identifier_str_mv Vera Janavel, Gustavo L.; De Lorenzi, Andrea; Cortés, Claudia; Olea, Fernanda Daniela; Cabeza Meckert, Patricia; et al.; Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion; John Wiley & Sons Ltd; Journal Of Gene Medicine; 14; 4; 4-2012; 279-287
1099-498X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/jgm.1608
info:eu-repo/semantics/altIdentifier/doi/10.1002/jgm.1608
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
dc.publisher.none.fl_str_mv John Wiley & Sons Ltd
publisher.none.fl_str_mv John Wiley & Sons Ltd
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 12.982451

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