| Project/Area Number |
10557068
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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 | 展開研究 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
KITAKAZE Masafumi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20294069)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Hideyuki Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70167435)
TADA Michihiko Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (90093434)
HORI Masatsugu Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (20124779)
NISHIDA Masashi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助手 (40283783)
MASUYAMA Tohru Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70273670)
宮崎 純一 大阪大学, 医学部, 教授 (10200156)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | Adenosine / Ecto-5'-Nucleotidase / Acute Myocardial Infarction / cDNA array / Adenosine Receptor Antagonists / Chronic Heart Failure / ecto-5' nucleotidase / 慢性心不全 / アデノシン産生増強薬 / 左室駆出率 / 運動耐容能 / ccto-5´-nuclcotidase / 遺伝子発現ラット |
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| Research Abstract |
We have previously revealed that adenosine mediates cardioprotection against ischemic and reperfusion injury. In the present study, we have been investigating the role of adenosine in ischemic and non- ischemic heart diseases from the basic and clinical aspects.
First of all, we tested the gene expression in the ischemic and non- ischemic heart failure and we tested the role of adenosine in the gene expression. This is because it is important to know the pathophysiology of ischemic hearts to protect the hearts against ischemic and reperfusion injury. However, many cardiologists have investigated only a few substances once using Northern or Western blot analysis to clarify the pharmacological effect on the diseased hearts. However, many substances simultaneously contribute to the pathophysiology of diseased hearts. cDNA array technique has recently developed as a novel method to evaluate much gene expression at once. We performed cDNA array to examine how many and what kind of genes are
… More
changed in the diseased hearts using cDNA array with and without administration of an adenosine receptor inhibitor. Cardiac expression of many genes was regulated by ischemic, mechanical and neurohumoral stress. Endogenous adenosine modulated almost half of these regulated genes in the ischemic hearts.
Second, we evaluated the effect of ATP, a precursor of adenosine, to limit the infarct size in the patients with acute myocardial infarction. Intracoronary injection of ATP was revealed to limit the infarct size.
Third, we investigated the role of adenosine in chronic heart failure because chronic heart failure is the final common end- stage of cardiovascular diseases. We evaluated the process of induction of ecto- 5' -nucleotidase during the development of heart failure with the heart failure model of Syrian Hamster. At the compensatory period of chronic heart failure ecto- 5' -nucleotidase activity is enhanced, but ecto- 5'- nucleotidase activity was decreased in decompensated heart failure.
Taken together, we have revealed that adenosine potently attenuates ischemic and non- ischemic heart failure, which may propose a new paradigm for the adenosine therapy of chronic heart failure. Less
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