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(Circulation. 2002;105:1226.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Administration of a Decoy Against the Activator Protein-1 Binding Site Suppresses Neointimal Thickening in Rabbit Balloon-Injured Arteries

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

From the Department of Surgery and Science, Graduate School of Medical Sciences and Division of Pathophysiological and Experimental Pathology (Y.Y.), Kyushu University, Fukuoka, Japan.

Correspondence to Kimihiro Komori, MD, PhD, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail komori{at}surg2.med.kyushu-u.ac.jp

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-ß₁ 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.

Key Words: proteins • balloon • restenosis • muscle, smooth • gene therapy

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