Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 33, Issue 3, Pages 575-580Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1006/jmcc.2000.1322
Keywords
gene therapy; VEGF; adenovirus; vascular permeability; phosphodiesterase inhibitors
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Funding
- NHLBI NIH HHS [P50 HL 52307] Funding Source: Medline
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Current gene therapy models are limited by inadequate vector delivery. Increases in microvascular permeability have been shown to improve adenovirus-mediated gone 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 cs vivo model of coronary perfusion in rabbits. rue 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. (C) 2001 Academic Press.
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