| Project/Area Number |
11307012
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SASAYAMA Shigetake Kyoto University, Dept. of Cardiovasc. Med., Professor, 医学研究科, 教授 (70109007)
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| Co-Investigator(Kenkyū-buntansha) |
KIHARA Yasuki Kyoto University, Dept. of Cardiovasc. Med., Assistant, 医学研究科, 助手 (40214853)
MATSUMORI Akira Kyoto University, Dept. of Cardiovasc. Med., Associate Professor, 医学研究科, 助教授 (70135573)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥37,500,000 (Direct Cost: ¥37,500,000)
Fiscal Year 2000: ¥16,800,000 (Direct Cost: ¥16,800,000)
Fiscal Year 1999: ¥20,700,000 (Direct Cost: ¥20,700,000)
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| Keywords | heart failure / cytokine / p38 mitogen-activated protein kinase / MKK6 / apoptosis / oxidative stress / cardiac hypertrophy / myocardial infarction / トランスジェニック / マウス / PPAK |
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| Research Abstract |
We investigated the role of cytokines in the pathogenesis of cardiac injury using murine model of myocarditis, cardiac hypertrophy, and myocardial infarction. These data suggest that inflammatory cytokines play an important role in the development and progression of heart failure regardless of the cause of cardiac injury. Stress-activated MAPKs are one of the important signal cascade which regulate the expression of cytokines. Above all, p38MAPK is suggested to induce cardiac hypertrophy and apoptosis in responses to viral infection, pressure overload, and oxidative stress. This project is designed to clarify the in vivo role of p38MAPK cascade by transgenic model. First we tried to overexpress pMAPK in mouse. However it was embryonic lethal. Next, we developed a line of MKK6EE transgenic mouse. MKK6EE is a constitutively active from of MKK6, a MAPKK which regulates pMAPK.In the transgenic line, however, MKK6EE was detected only at mRNA level. No MKK6EE protein nor activity was detected. We further tried to make pressure-overload and myocardial infarction in that mice, but the extent of cardiac hypertrophy or the cardiac injury was not different. Thus, it was suggested that MKK6-p38 signaling is involved in the early development of embryo.
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