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Vascular endothelial growth factor-A gene electrotransfer promotes angiogenesis in a porcine model of cardiac ischemia

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Abstract

This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility. Arteriograms suggest growth of new arteries as early as 2 weeks after treatment in electrotransfer animals. There is a significant reduction of infarct area and left ventricular contractility is improved in GET-treated group compared with controls. There was no significant difference in mortality of animals treated with GET of plasmid encoding VEGF-A from the control groups. Gene delivery of plasmid encoding VEGF-A to ischemic myocardium in a porcine model can be accomplished safely with potential for myocardial repair and regeneration.

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Acknowledgements

We thank Dr Mark Jaroszeski of University of South Florida, Tampa, FL, USA for design and construction of the electrode arrays used for gene electrotransfer. We also thank RaShae Cooke, Danielle Tajirian, Ben Cuffee and Ann Nix for providing excellent veterinary care to the animals throughout this study. We also thank Dr Robert Strange Jr of Portsmouth Naval Facility, Portsmouth, VA, USA and Dr Paul D Mahoney of Sentara Heart Hospital, Norfolk, VA, USA for surgical and arteriogram acquisition training. Funding for this work came from the National Institutes of Health R33 HL005441. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. A A Bulysheva and B Hargrave: These authors contributed equally to this work.

Authors and Affiliations

  1. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA

    A A Bulysheva, B Hargrave, N Burcus, C G Lundberg & R Heller

  2. School of Medical Diagnostics and Translational Sciences, College of Health and Sciences, Old Dominion University, Norfolk, VA, USA

    B Hargrave & R Heller

  3. SoBran, Inc., Fairfax, VA, USA

    L Murray

Authors
  1. A A Bulysheva
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  2. B Hargrave
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  3. N Burcus
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  4. C G Lundberg
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  5. L Murray
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  6. R Heller
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Corresponding author

Correspondence to R Heller.

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The authors declare no conflict of interest.

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Bulysheva, A., Hargrave, B., Burcus, N. et al. Vascular endothelial growth factor-A gene electrotransfer promotes angiogenesis in a porcine model of cardiac ischemia. Gene Ther 23, 649–656 (2016). https://doi.org/10.1038/gt.2016.35

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