2000 Fiscal Year Final Research Report Summary
Effect of transfer of synthetic double-stranded cis-element "decoy" oligodeoxynucleotides(ODNs) on neointimal thickening.
| Project/Area Number |
11671166
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KOMORI Kimihiro Kyushu University Hospital, Lecturer, 医学部・附属病院, 講師 (40225587)
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| Co-Investigator(Kenkyū-buntansha) |
FURUYAMA Tadashi Kyushu University Hospital, Assistant, 医学部・附属病院, 医員
SYOJI Tetsuya Kyushu University Hospital, Assistant, 医学部・附属病院, 医員
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| Project Period (FY) |
1999 – 2000
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| Keywords | Intimal thickening / gene therapy / transcription factor / activator protein-1 / smooth muscle cells / decoy |
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| Research Abstract |
Background--Progressive neointimal thickening and restenosis remain major critical problems limiting the long-term efficacy of percutaneous transluminal coronary angioplasty or bypass surgery to treat subjects with vascular occlusive diseases. We examined the role of transfer of synthetic double-stranded cis-element "decoy" oligodeoxynucleotides(ODNs) in case of balloon injured rabbit carotid arteries and effects of these ODNs on neointimal thickening were investigated.
Methods and Results--Transfection of flurescein isothiocyante(FITC)-labeled ODNs, using the hemagglutinating virus of Japan(HVJ)-liposome method, resulted in widespread distribution of fluorescent nuclear signals over the entire medial layer, while direct transfer of unmodified FITC-labeled ODNs showed patchy and scattered distribution in balloon injured rabbit carotid arteries. The gel mobility shift revealed that AP-1 DNA binding was activated, and that the AP-1 decoy ODNs reduced AP-1 DNA binding activity, as a result of specific binding affinity to AP-1 in vivo. In morphometric analyses, AP-1 decoy ODNs led to a significant reduction in the neointimal area and a significant reduction in cell number of human aortic smooth muscle cells, under conditions of platelet-derived growth factor stimulation.
Conclusions--As AP-1 decoy ODNs transfection in vivo dramatically prevented neointimal thickening in balloon injured arteries, AP-1 may be an useful molecular target for gene therapy to reduce restenosis.
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