Document Detail


Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries.
MedLine Citation:
PMID:  11889018     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-beta(1) 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.
Authors:
Masazumi Kume; Kimihiro Komori; Takuya Matsumoto; Toshihiro Onohara; Kensuke Takeuchi; Yoshikazu Yonemitsu; Keizo Sugimachi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  105     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-03-12     Completed Date:  2002-03-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1226-32     Citation Subset:  AIM; IM    
Affiliation:
Department of Surgery and Science, Graduate School of Medical Sciences and Division of Pathophysiological and Experimental Pathology, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Balloon Dilatation / adverse effects
Binding Sites / drug effects
Binding, Competitive / drug effects
Carotid Artery Injuries*
Carotid Artery, Common / pathology
Carotid Stenosis / etiology,  pathology,  prevention & control*
Cell Count
Cell Division / drug effects
Cells, Cultured
DNA / metabolism
Disease Models, Animal
Fluorescein-5-isothiocyanate
Gene Therapy / methods*
Humans
Liposomes
Male
Muscle, Smooth, Vascular / cytology,  drug effects,  metabolism
Oligonucleotides / genetics,  metabolism,  pharmacology*
Rabbits
Sendai virus / genetics
Transcription Factor AP-1 / antagonists & inhibitors,  metabolism*
Transfection
Transforming Growth Factor beta / metabolism
Transforming Growth Factor beta1
Tunica Intima / drug effects*,  injuries,  metabolism
Chemical
Reg. No./Substance:
0/Liposomes; 0/Oligonucleotides; 0/TGFB1 protein, human; 0/Transcription Factor AP-1; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 3326-32-7/Fluorescein-5-isothiocyanate; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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