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

Abstract

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 ti..