PURPOSE: Nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-kappaB activity using balloon-injured arteries, and we introduced NF-kappaB 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-kappaB in balloon-injured arteries. In vivo transfection of decoy ODNs mediated by HVJ liposome abolished the NF-kappaB activity in injured arteries with specific binding affinity to NF-kappaB protein. Intimal hyperplasia of carotid artery after balloon injury was reduced by approximately 50% by NF-kappaB decoy transfection compared with buffer treatment or scrambled decoy transfection. CONCLUSION: Our results demonstrated involvement of NF-kappaB in intimal formation after arterial injury, and indicated that NF-kappaB can be an appropriate molecular target for anti-restenosis therapy.
PURPOSE: Nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-kappaB activity using balloon-injured arteries, and we introduced NF-kappaB 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-kappaB in balloon-injured arteries. In vivo transfection of decoy ODNs mediated by HVJ liposome abolished the NF-kappaB activity in injured arteries with specific binding affinity to NF-kappaB protein. Intimal hyperplasia of carotid artery after balloon injury was reduced by approximately 50% by NF-kappaB decoy transfection compared with buffer treatment or scrambled decoy transfection. CONCLUSION: Our results demonstrated involvement of NF-kappaB in intimal formation after arterial injury, and indicated that NF-kappaB can be an appropriate molecular target for anti-restenosis therapy.
Authors: S Kaul; B Cercek; J Rengstrom; X P Xu; M D Molloy; P Dimayuga; A K Parikh; M C Fishbein; J Nilsson; T B Rajavashisth; P K Shah Journal: J Am Coll Cardiol Date: 2000-02 Impact factor: 24.094
Authors: R Morishita; G H Gibbons; M Horiuchi; K E Ellison; M Nakama; L Zhang; Y Kaneda; T Ogihara; V J Dzau Journal: Proc Natl Acad Sci U S A Date: 1995-06-20 Impact factor: 11.205
Authors: H Tanaka; P Vickart; J R Bertrand; B Rayner; F Morvan; J L Imbach; D Paulin; C Malvy Journal: Nucleic Acids Res Date: 1994-08-11 Impact factor: 16.971
Authors: Manoj Bhasin; Zhen Huang; Leena Pradhan-Nabzdyk; Junaid Y Malek; Philip J LoGerfo; Mauricio Contreras; Patrick Guthrie; Eva Csizmadia; Nicholas Andersen; Olivier Kocher; Christiane Ferran; Frank W LoGerfo Journal: PLoS One Date: 2012-06-15 Impact factor: 3.240