| Inhibition of NFkappaB activation using cis-element 'decoy' of NFkappaB binding site reduces neointimal formation in porcine balloon-injured coronary artery model. | |
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MedLine Citation:
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PMID: 12595894 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Application of DNA technology to regulate the transcription of disease-related genes has important therapeutic potential. The transcription factor NFkappaB plays a pivotal role in the transactivation of inflammatory and adhesion molecule genes, leading to vascular lesion formation. Double-stranded DNA with high affinity for NFkappaB may be introduced as 'decoy' cis elements to bind NFkappaB and block the activation of genes mediating inflammation, resulting in effective drugs for treating intimal hyperplasia. In this study, we tested the feasibility of NFkappaB decoy therapy to treat neointimal formation in a porcine coronary artery balloon injury model as a pre-clinical study. An angioplasty catheter was introduced into the left anterior descending coronary artery of the pig to cause vascular injury. First, we tested the feasibility of transfection of FITC-labeled NFkappaB decoy ODN using a hydrogel balloon catheter. Fluorescence due to NFkappaB decoy ODN could be detected throughout the medial layer. Therefore, we transfected NFkappaB decoy ODN into the balloon-injured LAD using a hydrogel catheter. Histological evaluation demonstrated that the neointimal area in the balloon-injured artery was significantly reduced by NFkappaB decoy ODN as compared to scrambled decoy ODN at 1 week after single transfection, accompanied by a significant reduction in PCNA-positive stained cells (P < 0.01). Interestingly, the reduction of ICAM-positive staining was observed, accompanied by the inhibition of migration of macrophages. Of importance, intravascular ultrasound (IVUS) confirmed that neointimal area in the balloon-injured artery was significantly reduced by NFkappaB decoy ODN at 4 weeks after transfection (P < 0.01). Interestingly, the inhibition of neointimal area was only limited to the lesion transfected with NFkappaB decoy ODN, while other lesions without NFkappaB decoy ODN demonstrated a marked increase in neointimal formation. Here, we report the successful in vivo transfer of NFkappaB decoy ODN using a hydrogel catheter to inhibit vascular lesion formation in balloon-injured porcine coronary artery. |
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Authors:
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K Yamasaki; T Asai; M Shimizu; M Aoki; N Hashiya; H Sakonjo; H Makino; Y Kaneda; T Ogihara; R Morishita |
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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: 10 ISSN: 0969-7128 ISO Abbreviation: Gene Ther. Publication Date: 2003 Feb |
Date Detail:
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Created Date: 2003-02-21 Completed Date: 2003-04-14 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: 356-64 Citation Subset: IM |
Affiliation:
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Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angioplasty, Transluminal, Percutaneous Coronary
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adverse effects* Animals Binding Sites / genetics Coronary Restenosis / metabolism, pathology, therapy* Coronary Vessels / metabolism*, pathology, ultrasonography Male Models, Animal Muscle, Smooth, Vascular / metabolism, pathology NF-kappa B / metabolism* Oligodeoxyribonucleotides / administration & dosage* Swine, Miniature Tunica Intima / metabolism*, pathology Ultrasonography, Interventional |
| Chemical | |
Reg. No./Substance:
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0/NF-kappa B; 0/Oligodeoxyribonucleotides |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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