부산대학교 도서관

Purpose Nuclear factor-IoB (NF-IoB) plays a critical role in inflammation-related reactions, and is also found in the injured arterial wall. The purpose of this study was to introduce synthetic double-stranded cis-element "decoy" oligonucleotides (ODNs) into the arterial wall using the hemagglutinating virus of Japan (HVJ) liposome, and to investigate the inhibitory potential of decoy ODN against balloon injury-induced intimal hyperplasia by reducing NF-IoB activity. Methods Fluorescein isothiocyanate (FITC)-labeled decoy ODNs using the HVJ-liposome method were tranfected in balloon-injured rabbit carotid arteries. We then performed electrophoretic mobility shift assay to examine NF-IoB activity using balloon-injured arteries, and we introduced NF-IoB decoy into balloon-injured arteries. Results Transfection of FITC-labeled decoy ODNs by using the HVJ-liposome method demonstrated highly efficient protein expression with diffuse, frequent, and widespread nuclear signals over the entire medial layer, while the same amount of naked ODNs showed much less efficiency with scattered distribution of fluorescence in balloon-injured carotid arteries. Electrophoretic mobility shift assay showed activation of NF-IoB in balloon-injured arteries. In vivo transfection of decoy ODNs mediated by HVJ liposome abolished the NF-IoB activity in injured arteries with specific binding affinity to NF-IoB protein. Intimal hyperplasia of carotid artery after balloon injury was reduced by approximately 50% by NF-IoB decoy transfection compared with buffer treatment or scrambled decoy transfection. Conclusion Our results demonstrated involvement of NF-IoB in intimal formation after arterial injury, and indicated that NF-IoB can be an appropriate molecular target for anti-restenosis therapy.