4.5 Article

Adenoviral infection or deferoxamine? Two approaches to overexpress VEGF in β-cell lines

Journal

JOURNAL OF DRUG TARGETING
Volume 17, Issue 6, Pages 415-422

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/10611860902929832

Keywords

beta-cells; angiogenesis; VEGF; adenovirus; deferoxamine; hypoxia; HIF-1 alpha; apoptosis; gene therapy; insulin

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Rapid and adequate revascularization of transplanted islets is important for their survival and function during transplantation. Vascular endothelial growth factor (VEGF) could play a critical role with respect to islet revascularization. The aim of this study was to compare two strategies that are used to overexpress VEGF in beta-cells: (1) gene therapy through adenoviral infection and (2) a pharmacological approach using deferoxamine (DFO). beta-Cell lines from rat insulinoma (RINm5F) were either infected using an adenovirus encoding the gene of human VEGF 165 or incubated with DFO. One day after treatment, the viability of RINm5F cells was preserved with 10 mu mol/L of DFO (103.95 +/- 5.66% toward control; n=4). In addition, adenoviral infection maintained the viability of cells for all the concentrations used. In both treatments, overexpression of VEGF was in a comparable level. Finally, the ratio of Bax/Bcl-2 indicated that the apoptosis increased in infected beta-cells whereas treatment with DFO seems to be antiapoptotic. Our results suggest that the use of DFO could be a realistic approach to improve the vascularization of islets during transplantation.

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