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

M. Lee, J. Rentz, M. Bikram, S. Han, D. A. Bull, S. W. Kim

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

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 myocardium. 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.

Original languageEnglish (US)
Pages (from-to)1535-1542
Number of pages8
JournalGene Therapy
Volume10
Issue number18
DOIs
StatePublished - Sep 2003
Externally publishedYes

Keywords

  • Hypoxia
  • Ischemic myocardium
  • Nonviral gene therapy
  • Vascular endothelial growth factor
  • Water-soluble lipopolymer

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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