| Molecular strategy using cis-element 'decoy' of E2F binding site inhibits neointimal formation in porcine balloon-injured coronary artery model. | |
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MedLine Citation:
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PMID: 11948373 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Gene therapy Volume: 9 ISSN: 0969-7128 ISO Abbreviation: Gene Ther. Publication Date: 2002 Apr |
Date Detail:
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Created Date: 2002-04-11 Completed Date: 2002-05-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: England |
Other Details:
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Languages: eng Pagination: 488-94 Citation Subset: IM |
Affiliation:
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Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/E2F Transcription Factors; 0/Oligodeoxyribonucleotides; 0/Transcription Factors |
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