| Project/Area Number |
09044299
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
OGIHARA Toshio Osaka University Faculty of Medicine, Professor, 医学部, 教授 (60107042)
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| Co-Investigator(Kenkyū-buntansha) |
DZAU Victor J Harvard University Faculty of Medicine, Professor, 医学部, 教授
MORISHITA Ryuichi Osaka University Faculty of Medicine, Associate Professor, 医学部, 助教授 (40291439)
MORIGUCHI Atushi Osaka University Faculty of Medicine, Assistant Professor, 医学部, 助手 (10273666)
KANEDA Yasufumi Osaka University Faculty of Medicine, Professor, 医学部, 教授 (10177537)
HIGAKI Jituo Osaka University Faculty of Medicine, Associate Professor, 医学部, 助教授 (70189744)
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| Project Period (FY) |
1997 – 1998
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| Keywords | gene therapy / HGF / decoy / restenosis / peripheral arterial disease |
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| Research Abstract |
Recently, gene therapy has been center of interests in the treatment of cardiovascular disease. One of major targets for gene therapy is restenosis after angioplasty. To achieve the complete inhibition of neointimal formation, we have identified cell cycle regulatory proteins as a target. Application of decoy strategy to regulate the transcription of disease-related genes has important therapeutic potentials. Thus, decoy against transcription factor E2F that is essential for cell proliferation resulted in the complete inhibition of neointimal formation up to 8 weeks after transfection. We also employed porcine coronary artery balloon injury model. Transfection of E2F decoy ODN using hydrogel catheter resulted in a significant inhibition of neointimal formation. Currently, we plan to start human gene therapy trial using E2F decoy to treat restenosis after angioplasty.
Alternatively, we also focused on the therapeutic angiogenesis strategy using human hepatocyte growth factor (HGF) gene. Number of vessels in rat hindlimb transfected with HGF gene was significantly. increased, accompanied by a significant increase in blood flow. Thus, we provided direct in vivo evidence for angiogenesis induced by HGF gene in rat ischemic hindlimb model. Based upon these findings, we submitted the clinical protocol of human gene therapy using HGE to treat peripheral arterial disease to Osaka University.
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