Gene transfer using the mature form of VEGF-D reduces neointimal thickening through nitric oxide-dependent mechanism.

Autor: Rutanen, J., Turunen, A.-M., Teittinen, M., Rissanen, T. T., Heikura, T., Koponen, J. K., Gruchala, M., Inkala, M., Jauhiainen, S., Hiltunen, M. O., Turunen, M. P., Stacker, S. A., Achen, M. G., Ylä-Herttuala, S.
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Zdroj: Gene Therapy; Jun2005, Vol. 12 Issue 12, p980-987, 8p
Abstrakt: Gene transfer to the vessel wall using vascular endothelial growth factors (VEGFs) has shown therapeutic potential for the treatment of restenosis. In this study, we evaluated the effect of catheter-mediated adenoviral (Ad) gene transfer of the mature form of VEGF-D (VEGF-DΔNΔC) in balloon-denuded cholesterol-fed rabbit aorta. AdLacZ was used as a control. Transduced VEGF-DΔNΔC mRNA was detectable in the arterial wall with RT-PCR at 6, 14 and 28 days. Gene transfer efficiency as detected with X-gal staining 6 days after the AdLacZ transduction was 1.91±1.32% in intima. AdVEGF-DΔNΔC gene transfer led to 52% reduction in intima/media ratio (I/M) as compared to the AdLacZ controls at 14 days time point. At 6 days there were no differences in I/M, but the number of macrophages in the vessel wall was 85% lower in the AdVEGF-DΔNΔC group as compared to the controls. The therapeutic effect was no longer detectable 28 days after the gene transfer. The therapeutic effect of VEGF-DΔNΔC was nitric oxide (NO)-dependent as the feeding of NO synthase inhibitor, L-NAME, blocked the reduction in intimal thickening. It is concluded that AdVEGF-DΔNΔC gene transfer reduces intimal thickening and macrophage influx into the vessel wall in balloon-denuded rabbit aortas.Gene Therapy (2005) 12, 980–987. doi:10.1038/sj.gt.3302489 Published online 10 March 2005 [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index