Phosphodiesterase inhibitor-mediated potentiation of adenovirus delivery to myocardium

Koichi Nagata, Eduardo Marbán, John H. Lawrence, Kevin J. Donahue

Research output: Contribution to journalArticle

Abstract

Current gene therapy models are limited by inadequate vector delivery. Increases in microvascular permeability have been shown to improve adenovirus-mediated gene transfer to ex vivo and in vivo models. We explored the intracellular mechanism underlying the permeabilizing effects of vascular endothelial growth factor (VEGF). Using an ex vivo model of coronary perfusion in rabbits, we found a dose-response relationship between VEGF and the efficiency of adenoviral gene transfer. Inhibitors of nitric oxide synthase and guanylate cyclase prevented the VEGF effect, and analogues of nitric oxide and cGMP mimicked the effect. Co-administration of phosphodiesterase-5 inhibitors and VEGF caused a synergistic increase in gene delivery. These results can be readily applied to existing models to further optimize vector delivery for gene therapy.

Original languageEnglish (US)
Pages (from-to)575-580
Number of pages6
JournalJournal of Molecular and Cellular Cardiology
Volume33
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Adenovirus
  • Gene therapy
  • Phosphodiesterase inhibitors
  • Vascular Permeability
  • VEGF

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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