Project/Area Number |
06404047
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Thoracic surgery
|
Research Institution | Osaka University |
Principal Investigator |
MATSUDA Hikaru Osaka University, Medical School, Professor, 医学部, 教授 (00028614)
|
Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Kazihiro Osaka University, Medical School, Assistant Professor, 医学部, 助手 (90171842)
KANEDA Yasufumi Osaka University, ICBM., Associate Professor, 細胞生体工学センター, 助教授 (10177537)
SAWA Yoshiki Osaka University, Medical School, Assistant Professor, 医学部, 助手 (00243220)
SHIRAKURA Ryota Osaka University, Medical School, Professor, 医学部, 教授 (00116047)
|
Project Period (FY) |
1994 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥20,300,000 (Direct Cost: ¥20,300,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1995: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1994: ¥15,200,000 (Direct Cost: ¥15,200,000)
|
Keywords | gene transfection / myocardial protection / ischemia-reperfusion / cardiac preservation / heat shock protein / DNA engineering / 心保存法 / ストレス蛋白 / HVJ-liposome法 / 心筋虚血耐性 / DNA組みかえ / Heat shock Protein / 心筋虚血再灌流障害 / 遺伝子治療 |
Research Abstract |
To develop a myocardial protection against is chemia-reperfusion injury, many kinds of pharmacological approaches have been tried. But they appear to have limited efficacy even now. Recently, another approach which uses self-preservation systems, such as is chemic preconditioning and heat shock, is expected to develop a further advanced myocardial protection. HSP70 is reported to be induced under various forms of stress such as ischemis, heat shock, or drug administration and enhance myocardial tolerance to ischemia-reperfusion injury. The object of this study is to develop a novel method for myocardial protection with gene transfection through enforcing the self-preservation system, such as HSP70. First, we isolated the role of HSP70 in coronary endothelial cells and in cardiac myocytes under conditions of ischemia-reperfusion injury using in vitro gene transfection. Next, we developed the oprimal method for in vivo gene transfection to whole heart by intracoronary infusion of HVJ-liposome. Then, we demonstrated that it is possible to introduce HSP70 into the entire heart with this gene transfection method and enhance myocardial tolerance to ischemia-reperfusion injury. These results showed the possibility of clinical application of gene therapy (long-term cardiac preservation) with HSP70 to ischemia-reperfusion injury of the heart.
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