Inhibition of NFκB activation using cis-element ‘decoy’ of NFκB binding site reduces neointimal formation in porcine balloon-injured coronary artery model

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Abstract
Application of DNA technology to regulate the transcription of disease-related genes has important therapeutic potential. The transcription factor NFκB plays a pivotal role in the transactivation of inflammatory and adhesion molecule genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for NFκB may be introduced as ‘decoy’ cis elements to bind NFκB and block the activation of genes mediating inflammation, resulting in effective drugs for treating intimal hyperplasia. In this study, we tested the feasibility of NFκB decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model as a pre-clinical study. An angioplasty catheter was introduced into the left anterior descending coronary artery of the pig to cause vascular injury. First, we tested the feasibility of transfection of FITC-labeled NFκB decoy ODN using a hydrogel balloon catheter. Fluorescence due to NFκB decoy ODN could be detected throughout the medial layer. Therefore, we transfected NFκB decoy ODN into the balloon-injured LAD using a hydrogel catheter. Histological evaluation demonstrated that the neointimal area in the balloon-injured artery was significantly reduced by NFκB decoy ODN as compared to scrambled decoy ODN at 1 week after single transfection, accompanied by a significant reduction in PCNA-positive stained cells (Pin vivo transfer of NFκB decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery.