Abstract 14963: Prevention of Neointimal Hyperplasia After Angioplasty Using NF-kappaB Decoy Oligodeoxynucleotides-Coated Balloon Catheter in Rabbit Restenosis Model
Restenosis after endovascular intervention is a major limitation of this minimally invasive technique and hampers the procedure's efficacy for treating cardiovascular disease. To overcome this problem, we have focused on the transcription factor, NFκB, which plays an important role in the transcription of a variety of genes, primarily those related to inflammation. We hypothesized that the inhibition of NFκB binding activity using decoy oligodeoxynucleotides (ODN) might be an effective approach to prevent neointimal formation after percutaneous transluminal angioplasty (PTA). NFκB decoy ODN were entrapped into a biodegradable PLGA nanosphere. This nanosphere was coated with chitosan, resulting in generating positive charges. As the balloon surface of the catheter was negatively charged by hydrophilic coating polymer, PLGA nanospheres could electrostatically bind to the balloon surface. Using this NFκB decoy ODN-coated catheter, we examined the effect of local application of NFκB decoy ODN on neointimal formation after angioplasty in a rabbit restenosis model. PTA was performed in the right carotid artery at 4 weeks after denudation of endothelium. Distribution study demonstrated that FITC-labeled nanospheres could be detected in neointima until 3 weeks after PTA. In addition, EMSA study showed that NFκB activity was significantly inhibited by NFκB decoy ODN transfer. Four weeks after PTA, the treatment with NFκB decoy ODN significantly inhibited neointimal hyperplasia and reduced intima-to-media ratio as compared to control or scrambled decoy ODN treatment. Immunohistochemical staining revealed that the treatment with NFκB decoy ODN inhibited the macrophage recruitment in neointima. In addition, NFκB decoy ODN transfer suppressed the expression of cyclin A and PCNA in vascular smooth muscle cells (VSMC), whereas re-endothelialization was not inhibited at the site of PTA. Here, we demonstrated that nanoparticle-mediated local administration of NFκB decoy ODN inhibited the development of neointimal hyperplasia after angioplasty, followed by suppression of inflammatory response and proliferating activity in VSMC. The present study raises the possibility of a novel strategy for prevention of restenosis after angioplasty.
- © 2011 by American Heart Association, Inc.