Post-translational regulation of a hypoxia-responsive VEGF plasmid for the treatment of myocardial ischemia

Young Wook Won, Arlo N. McGinn, Minhyung Lee, Kihoon Nam, David A. Bull, Sung Wan Kim

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) gene therapy to promote therapeutic angiogenesis has been advanced as an alternative treatment for myocardial ischemia. The unregulated expression of VEGF and the use of viral vectors, however, have slowed the clinical development of angiogenic gene therapy. The development of clinically beneficial angiogenic gene therapy requires a disease-specific gene expression system and an efficient non-viral gene carrier. To address these requirements, we developed a new post-translationally regulated hypoxia-responsible VEGF plasmid, pβ-SP-ODD-VEGF, and a dendrimer-type bio-reducible polymer, PAM-ABP. The efficacy of VEGF gene therapy with the PAM-ABP/pβ-SP-ODD-VEGF was evaluated and compared to the RTP-VEGF plasmid, a previously constructed hypoxia-inducible plasmid, in an ischemia/reperfusion (I/R) rat model. Cine magnetic resonance imaging was used to analyze the ischemia/reperfusion rats treated with either the PAM-ABP/pβ-SP-ODD-VEGF or the PAM-ABP/RTP-VEGF. The PAM-ABP/pβ-SP-ODD-VEGF treatment more effectively protected cardiomyocytes against apoptosis, preserved left ventricular (LV) function, and prevented LV remodeling compared to the PAM-ABP/RTP-VEGF-treated rats. These results suggest that the pβ-SP-ODD-VEGF with PAM-ABP may be efficacious in the treatment of acute ischemic heart disease.

Original languageEnglish (US)
Pages (from-to)6229-6238
Number of pages10
JournalBiomaterials
Volume34
Issue number26
DOIs
StatePublished - Aug 2013
Externally publishedYes

Keywords

  • Gene therapy
  • Myocardial infarct
  • PAM-ABP
  • VEGF

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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