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Hypoxia-inducible VEGF gene delivery to ischemic myocardium using water-soluble lipopolymer

Gene Therapy volume 10, pages 1535–1542 (2003)Cite this article

Abstract

Therapeutic angiogenesis with gene encoding vascular endothelial growth factor (VEGF) is a new potential treatment in cardiovascular disease. However, unregulated VEGF-mediated angiogenesis has the potential to promote tumor growth, accelerate diabetic proliferative retinopathy, and promote rupture of atherosclerotic plaque. To be safe and effective, gene therapy with VEGF must be regulated. To limit the risk of pathological angiogenesis, we developed a hypoxia-inducible VEGF gene therapy system using the erythropoietin (Epo) enhancer and water-soluble lipopolymer (WSLP). pEpo-SV-VEGF or pSV-VEGF-Epo was constructed by insertion of the Epo enhancer upstream of the Simian Virus 40 (SV40) promoter or downstream of the poly(A) signal of pSV-VEGF. In vitro transfection showed that pEpo-SV-VEGF, not pSV-VEGF-Epo, induced the VEGF expression in hypoxic cells. In addition, the VEGF protein, which was produced from the Epo-SV-VEGF-transfected and hypoxia-incubated cells, was able to enhance the proliferation of the endothelial cells. Injection of the pEpo-SV-VEGF/WSLP complex showed that the expression of VEGF was induced in ischemic myocardium, compared to normal myo-cardium. Therefore, with the localized induction of VEGF and the low cytotoxicity of WSLP, the pEpo-SV-VEGF/WSLP system may be helpful to eventually treat ischemic heart disease.

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Acknowledgements

We thank Expression Genetics Inc. for financial support and Thomas Skidmore and Michael Skidmore for technical assistance. This work was supported by National Institutes of Health Grant HL65477.

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Authors and Affiliations

  1. Clinical Research Center, College of Medicine, Inha University, Incnan, Korea

    M Lee

  2. Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT, USA

    M Bikram, S Han & S W Kim

  3. Department of Surgery, Division of Cardiothoracic Surgery, University of Utah Health Sciences Center, Salt Lake City, UT, USA

    J Rentz & D A Bull

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  1. M Lee
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  2. J Rentz
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Lee, M., Rentz, J., Bikram, M. et al. Hypoxia-inducible VEGF gene delivery to ischemic myocardium using water-soluble lipopolymer. Gene Ther 10, 1535–1542 (2003). https://doi.org/10.1038/sj.gt.3302034

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