| Project/Area Number |
13470147
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
SATO Hiroshi (2002) Osaka University, Graduate School of Medicine, Assistant Prof., 医学系研究科, 助手 (10294092)
佐藤 秀幸 (2001) 大阪大学, 医学系研究科, 助手 (70167435)
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| Co-Investigator(Kenkyū-buntansha) |
KUZUYA Tsunehiko Osaka Shoin Womens' College, Professor., 学芸学部, 教授 (80150340)
HORI Masatsugu Osaka University, Graduate School of Medicine, Professor., 医学系研究科, 教授 (20124779)
KITAKAZE Masafumi National Cardiovascular Center, Division of Physiological Examination, Director., 生理機能検査部, 部長(研究職) (20294069)
MIYAZAKI Jun-ichi Osaka University, Graduate School of Medicine, Professor., 医学系研究科, 教授 (10200156)
TAKEDA Hiroshi Osaka University, Graduate School of Medicine, Professor., 医学系研究科, 教授 (20127252)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2001: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | PKC / ecto-5'-nucleotidase / PKA / KATP Channels / P70S6 Kinase / P38 MAP Kinase / Preconditioning / J-WIND / アデノシン / 一酸化窒素(NO) / Rhoキナーゼ / プロテインキナーゼC / プロテインキナーゼA / J-WIND試験 / 心保護作用 / 心筋梗塞 / p38MAPキナーゼ / HSP27 / 多施設臨床試験 / KATPチャネル開口剤 |
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| Research Abstract |
1. We have successfully developed the transgenic mice overexpressing the adenosine producing enzyme (ecto-5'-nucleotidase). Examination of these mice with cardiac ischemia and reperfusion resulted in smaller infarct size than that of control group. This effect was completely abolished by the adenosine receptor antagonist (8-SPT). The microarray analysis of the ischemic control myocardium in vivo showed the 230positive clones of m-RNA, including that of ecto-5'-nucleotidase in upper grade. These results show that adenosine is an endogenous cardioprotective agent and the exogenous treatment with adenosine could be a cardioprotective strategy.
2. In the anesthetized canine model, preconditioning procedure markedly reduced infarct size afforded by 90-minutes of ischemia and 6-hours of reperfusion. This effect was completely abolished by preischemic PKC inhibition, preischemic p38MAPK inhibition, or KATP channel blockade. Preconditioning translocated HSP27 from cytosol to membrane and myofibril that was inhibited by preischemic p38MAPK inhibition. We also found that PKA and Rho-kinase also take park in the cardioprotective mechanism of preconditioning.
3. We conducted COAT study, which examined the cardioprotective effect by superacute injection of ATP analogue. This study enrolled about 40 patients with acute myocardial infarction, and revealed the positive cardioprotective effect after 1 year. We are also conducting J-WIND study, examinating the cardioprotective effect by superacute injecti
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