Document Detail


Molecular strategy using cis-element 'decoy' of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model.
MedLine Citation:
PMID:  11948373     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transcription factor E2F plays a pivotal role in the transactivation of cell cycle regulatory genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for E2F as 'decoy' cis elements may block the activation of genes mediating the cell cycle, resulting in an effective therapeutic agent for treating intimal hyperplasia. In this study, we tested the feasibility of E2F decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model. An angioplasty catheter was inserted in the left anterior descending coronary artery of pigs to cause vascular injury. Initially, we tested the feasibility of transfection of FITC-labeled E2F decoy ODN using a hydrogel balloon catheter. Fluorescence due to E2F decoy ODN could be detected throughout the medial layer. Therefore, we transfected E2F decoy ODN into the balloon-injured artery using hydrogel catheter. Of importance, intravascular ultrasound (IVUS) and histological evaluation demonstrated that plaque area in the balloon-injured artery was significantly reduced by E2F decoy ODN compared with mismatched decoy ODN at 1 month after a single transfection (P < 0.01). In contrast, luminal and total vessel areas were significantly increased in vessels treated with E2F decoy ODN as compared with mismatched decoy. Endothelial function after angioplasty was not affected by E2F decoy transfection. Finally, we tested the acute toxicity of E2F decoy ODN in monkeys, and no apparent side-effects were detected. Here, we report the successful in vivo transfer of E2F decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery without any apparent side-effects.
Authors:
T Nakamura; R Morishita; T Asai; N Tsuboniwa; M Aoki; H Sakonjo; K Yamasaki; N Hashiya; Y Kaneda; T Ogihara
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gene therapy     Volume:  9     ISSN:  0969-7128     ISO Abbreviation:  Gene Ther.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-11     Completed Date:  2002-05-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  488-94     Citation Subset:  IM    
Affiliation:
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
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MeSH Terms
Descriptor/Qualifier:
Angioplasty, Transluminal, Percutaneous Coronary
Animals
Binding Sites
Cell Cycle
Cell Cycle Proteins*
Coronary Disease / pathology,  therapy
Coronary Restenosis / pathology,  prevention & control*
DNA-Binding Proteins*
E2F Transcription Factors
Gene Therapy / methods*
Haplorhini
Male
Models, Animal
Oligodeoxyribonucleotides / metabolism
Swine, Miniature
Transcription Factors / genetics*,  metabolism
Transfection / methods*
Tunica Intima / pathology*
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/E2F Transcription Factors; 0/Oligodeoxyribonucleotides; 0/Transcription Factors

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


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