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.creatorVera Janavel, Gustavo L.
dc.creatorDe Lorenzi, Andrea
dc.creatorCortés, Claudia
dc.creatorOlea, Fernanda Daniela
dc.creatorCabeza Meckert, Patricia
dc.creatorBercovich, Andrés
dc.creatorCriscuolo, Marcelo
dc.creatorLaguens, Rubén
dc.creatorCrottogini, Alberto Jose
dc.date2012-04
dc.date.accessioned2023-08-31T00:32:04Z
dc.date.available2023-08-31T00:32:04Z
dc.identifierhttp://hdl.handle.net/11336/192882
dc.identifierVera 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
dc.identifier1099-498X
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8543528
dc.descriptionBackground: 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.
dc.descriptionFil: Vera Janavel, Gustavo L.. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
dc.descriptionFil: De Lorenzi, Andrea. Fundación Favaloro; Argentina
dc.descriptionFil: Cortés, Claudia. Fundación Favaloro; Argentina
dc.descriptionFil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.descriptionFil: Cabeza Meckert, Patricia. Fundación Favaloro; Argentina
dc.descriptionFil: Bercovich, Andrés. Biosidus S. A.; Argentina
dc.descriptionFil: Criscuolo, Marcelo. Biosidus S. A.; Argentina
dc.descriptionFil: Laguens, Rubén. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina
dc.descriptionFil: Crottogini, Alberto Jose. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherJohn Wiley & Sons Ltd
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/jgm.1608
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/10.1002/jgm.1608
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subjectANGIOGENESIS
dc.subjectGENE THERAPY
dc.subjectMYOCARDIAL INFARCTION
dc.subjectREMODELING
dc.subjectSHEEP
dc.subjectVEGF
dc.subjecthttps://purl.org/becyt/ford/3.4
dc.subjecthttps://purl.org/becyt/ford/3
dc.titleEffect 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.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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