Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries

Masazumi Kume, Kimihiro Komori, Takuya Matsumoto, Toshihiro Onohara, Kensuke Takeuchi, Yoshikazu Yonemitsu, Keizo Sugimachi

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background - Transcription factor activator protein-1 (AP-1) is activated and upregulated in injured arterial smooth muscle cells in vivo, yet the exact role of the AP-1-related pathway in vascular disease in vivo has remained unclear. We examined the role of the transfer of synthetic double-stranded cis-element decoy oligodeoxynucleotides (ODNs) in balloon-injured rabbit carotid arteries and the effects of these ODNs on neointimal thickening. Methods and Results - Transfection of fluorescein isothiocyanate-labeled ODNs using the hemagglutinating virus of Japan liposome method resulted in widespread distribution of fluorescent nuclear signals over the entire medial layer in injured arteries. Gel mobility shift assay revealed that AP-1 DNA binding was activated and that the AP-1 decoy reduced AP-1 DNA binding activity as a result of specific binding affinity to AP-1 in vivo. In morphometric analyses, AP-1 decoy led to a significant reduction in the neointimal area and a significant reduction in cell number and transforming growth factor-β1 production of human aortic smooth muscle cells under conditions of platelet-derived growth factor stimulation. Conclusions - Because AP-1 decoy transfection in vivo dramatically prevented neointimal thickening in balloon-injured arteries, AP-1 may be a useful molecular target for gene therapy to reduce restenosis.

Original languageEnglish
Pages (from-to)1226-1232
Number of pages7
JournalCirculation
Volume105
Issue number10
DOIs
Publication statusPublished - Mar 12 2002

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Transcription Factor AP-1
Protein Binding
Arteries
Binding Sites
Rabbits
Oligodeoxyribonucleotides
Smooth Muscle Myocytes
Transfection
Sendai virus
DNA
Platelet-Derived Growth Factor
Transforming Growth Factors
Electrophoretic Mobility Shift Assay
Fluorescein
Vascular Diseases
Carotid Arteries
Liposomes
Genetic Therapy
Transcription Factors
Cell Count

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries. / Kume, Masazumi; Komori, Kimihiro; Matsumoto, Takuya; Onohara, Toshihiro; Takeuchi, Kensuke; Yonemitsu, Yoshikazu; Sugimachi, Keizo.

In: Circulation, Vol. 105, No. 10, 12.03.2002, p. 1226-1232.

Research output: Contribution to journalArticle

Kume, Masazumi ; Komori, Kimihiro ; Matsumoto, Takuya ; Onohara, Toshihiro ; Takeuchi, Kensuke ; Yonemitsu, Yoshikazu ; Sugimachi, Keizo. / Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries. In: Circulation. 2002 ; Vol. 105, No. 10. pp. 1226-1232.
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