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

研究成果: Contribution to journalArticle査読

43 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1226-1232
ページ数7
ジャーナルCirculation
105
10
DOI
出版ステータス出版済み - 3 12 2002

All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学
  • 生理学(医学)

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