In vivo reduction of the nuclear factor-κB activity using synthetic cis-element decoy oligonucleotides suppresses intimal hyperplasia in the injured carotid arteries in rabbits

Kensuke Takeuchi, Hiroyuki Itoh, Yoshikazu Yonemitsu, takuya matsumoto, Masazumi Kume, Kimihiro Komori, Yoshihiko Maehara

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Purpose. Nuclear factor-κB (NF-κB) 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-κB 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-κB activity using balloon-injured arteries, and we introduced NF-κB 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-κB in balloon-injured arteries. In vivo transfection of decoy ODNs mediated by HVJ liposome abolished the NF-κB activity in injured arteries with specific binding affinity to NF-κB protein. Intimal hyperplasia of carotid artery after balloon injury was reduced by approximately 50% by NF-κB decoy transfection compared with buffer treatment or scrambled decoy transfection. Conclusion. Our results demonstrated involvement of NF-κB in intimal formation after arterial injury, and indicated that NF-κB can be an appropriate molecular target for anti-restenosis therapy.

Original languageEnglish
Pages (from-to)575-583
Number of pages9
JournalSurgery today
Volume37
Issue number7
DOIs
Publication statusPublished - Jul 1 2007

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Tunica Intima
Sendai virus
Carotid Arteries
Liposomes
Oligonucleotides
Hyperplasia
Transfection
Arteries
Rabbits
Electrophoretic Mobility Shift Assay
Fluorescein
Wounds and Injuries
Buffers
Proteins
Fluorescence
Inflammation
Therapeutics
isothiocyanic acid

All Science Journal Classification (ASJC) codes

  • Surgery

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In vivo reduction of the nuclear factor-κB activity using synthetic cis-element decoy oligonucleotides suppresses intimal hyperplasia in the injured carotid arteries in rabbits. / Takeuchi, Kensuke; Itoh, Hiroyuki; Yonemitsu, Yoshikazu; matsumoto, takuya; Kume, Masazumi; Komori, Kimihiro; Maehara, Yoshihiko.

In: Surgery today, Vol. 37, No. 7, 01.07.2007, p. 575-583.

Research output: Contribution to journalArticle

Takeuchi, Kensuke ; Itoh, Hiroyuki ; Yonemitsu, Yoshikazu ; matsumoto, takuya ; Kume, Masazumi ; Komori, Kimihiro ; Maehara, Yoshihiko. / In vivo reduction of the nuclear factor-κB activity using synthetic cis-element decoy oligonucleotides suppresses intimal hyperplasia in the injured carotid arteries in rabbits. In: Surgery today. 2007 ; Vol. 37, No. 7. pp. 575-583.
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abstract = "Purpose. Nuclear factor-κB (NF-κB) 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-κB 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-κB activity using balloon-injured arteries, and we introduced NF-κB 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-κB in balloon-injured arteries. In vivo transfection of decoy ODNs mediated by HVJ liposome abolished the NF-κB activity in injured arteries with specific binding affinity to NF-κB protein. Intimal hyperplasia of carotid artery after balloon injury was reduced by approximately 50{\%} by NF-κB decoy transfection compared with buffer treatment or scrambled decoy transfection. Conclusion. Our results demonstrated involvement of NF-κB in intimal formation after arterial injury, and indicated that NF-κB can be an appropriate molecular target for anti-restenosis therapy.",
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AU - matsumoto, takuya

AU - Kume, Masazumi

AU - Komori, Kimihiro

AU - Maehara, Yoshihiko

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