
Plasmid-mediated vegf gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep
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ABSTRACT We have recently reported that in pigs with chronic myocardial ischemia heart transfection with a plasmid encoding the 165 isoform of human vascular endothelial growth factor
(p_VEGF__165_) induces an increase in the mitotic index of adult cardiomyocytes and cardiomyocyte hyperplasia. On these bases we hypothesized that _VEGF_ gene transfer could also modify the
evolution of experimental myocardial infarct. In adult sheep p_VEGF__165_ (3.8 mg, _n_=7) or empty plasmid (_n_=7) was injected intramyocardially 1 h after coronary artery ligation. After 15
days infarct area was 11.3±1.3% of the left ventricle in the VEGF group and 18.2±2.1% in the empty plasmid group (_P_<0.02). The mechanisms involved in infarct size reduction (assessed
in additional sheep at 7 and 10 days after infarction) included an increase in early angiogenesis and arteriogenesis, a decrease in peri-infarct fibrosis, a decrease in myofibroblast
proliferation, enhanced cardiomyoblast proliferation and mitosis of adult cardiomyocytes with occasional cytokinesis. Resting myocardial perfusion (99mTc-sestamibi SPECT) was higher in
VEGF-treated group than in empty plasmid group 15 days after myocardial infarction. We conclude that plasmid-mediated _VEGF_ gene transfer reduces myocardial infarct size by a combination of
effects including neovascular proliferation, modification of fibrosis and cardiomyocyte regeneration. Access through your institution Buy or subscribe This is a preview of subscription
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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS LOW DOSE ADENOVIRAL VAMMIN GENE TRANSFER
INDUCES MYOCARDIAL ANGIOGENESIS AND INCREASES LEFT VENTRICULAR EJECTION FRACTION IN ISCHEMIC PORCINE HEART Article Open access 03 December 2024 AAV2-VEGF-B GENE THERAPY FAILED TO INDUCE
ANGIOGENESIS IN ISCHEMIC PORCINE MYOCARDIUM DUE TO INFLAMMATORY RESPONSES Article Open access 07 February 2022 SAFETY AND BIODISTRIBUTION OF XC001 (ENCOBERMINOGENE REZMADENOVEC) GENE THERAPY
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Download references ACKNOWLEDGEMENTS This work was supported by grants from The René G Favaloro University Foundation and by grant PID #268 from the Argentine National Agency for Scientific
and Technological Promotion (ANPCyT), Secretariat for Technology, Science and Productive Innovation (SeTCIP). Drs Crottogini and Laguens are established Investigators of National Council for
Scientific and Technical Investigations (CONICET). We thank technicians Julio Martínez, Fabián Gauna and Marcela Álvarez, veterinarians María Besansón, Pedro Iguain and Marta Tealdo and
animal house personnel Juan Ocampo, Osvaldo Sosa and Juan Mansilla. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Physiology, Favaloro University, Buenos Aires, Argentina G
Vera Janavel & A Crottogini * Department of Pathology, Favaloro University, Buenos Aires, Argentina P Cabeza Meckert, L Cuniberti & R Laguens * Scientific Investigation Commission
(CIC), Buenos Aires Province, Argentina P Cabeza Meckert * Institute of Cardiology and Cardiovascular Surgery of the Favaloro Foundation, Buenos Aires, Argentina A Mele * Bio Sidus, Buenos
Aires, Argentina M Papouchado, N Fernández, A Bercovich, M Criscuolo & C Melo Authors * G Vera Janavel View author publications You can also search for this author inPubMed Google
Scholar * A Crottogini View author publications You can also search for this author inPubMed Google Scholar * P Cabeza Meckert View author publications You can also search for this author
inPubMed Google Scholar * L Cuniberti View author publications You can also search for this author inPubMed Google Scholar * A Mele View author publications You can also search for this
author inPubMed Google Scholar * M Papouchado View author publications You can also search for this author inPubMed Google Scholar * N Fernández View author publications You can also search
for this author inPubMed Google Scholar * A Bercovich View author publications You can also search for this author inPubMed Google Scholar * M Criscuolo View author publications You can also
search for this author inPubMed Google Scholar * C Melo View author publications You can also search for this author inPubMed Google Scholar * R Laguens View author publications You can
also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to R Laguens. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE
Vera Janavel, G., Crottogini, A., Cabeza Meckert, P. _et al._ Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep. _Gene Ther_ 13,
1133–1142 (2006). https://doi.org/10.1038/sj.gt.3302708 Download citation * Received: 20 July 2005 * Revised: 17 November 2005 * Accepted: 18 November 2005 * Published: 06 April 2006 * Issue
Date: 01 August 2006 * DOI: https://doi.org/10.1038/sj.gt.3302708 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a
shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * myocardial infarction * VEGF *
heart regeneration * cardiomyocytes