2002 Fiscal Year Final Research Report Summary
Expression and Role of Inflammatory Cytokines in Acute Myocardial Infarction -usingTNF, IL-1, Il-6 knock out mice-
| Project/Area Number |
13670742
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Showa University |
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Principal Investigator |
SUZUKI Hiroshi Showa University, School of Medicine Assistant Professor, 医学部, 助手 (90266106)
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| Co-Investigator(Kenkyū-buntansha) |
KOBA Shinji Showa University. School of Medicine Assistant Professor, 医学部, 助手 (20276546)
GESHI Eiichi Showa University, School of Medicine Associate Professor, 医学部, 助教授 (50192050)
KATAGIRI Takashi Showa University, School of Medicine Professor, 医学部, 教授 (90102293)
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| Project Period (FY) |
2001 – 2002
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| Keywords | TNF-α / IL-1β / IL-6 / Myocardial infarction / Knock out mouse / Cytokine |
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| Research Abstract |
1. Acute myocardial infarction model was made by ligation of left anterior descending coronary arteries of TNF-α knock out mice (KO) and wild type (WT) mice. At 1, 3 and 7 days after infarction, cardiac ultrasound was performed, and the heart was excised for histological. immunohistochemical and morphological analysis.
2. Tissue levels of TNF-α and IL-6were increased in infarcted and non-infarcted areas in WT at 1 day after infarction and increased more at 3 days.
3. In ultrasound study, end-diastolic diameter was smaller in KO than in WT, and fractional shortening was higher in KO than WT at 3 and 7 days after infarction. Infiltration of inflammatory cells was observed from 1 day, and infiltration of macrophages were prominent at 3 days in histological examination, those of which were less in KO than WT in any period. Myocardial necrosis was prominent at 3 days, and wall thinning and left ventricular enlargement were observed at 7 days. In immnunohistochemical analysis, expression of metalloproteinase 2, 9, 13 was observed in infiltrating cells and cardiomyocytes in infracted and peri-infarcted areas at 1 day and prominent at 3 and 7 days. Those expressions were less in KO than in WT in any period. Furthermore, TUNEL positive cells representing apoptotic cells were less in KO than in WT in peri-infarcted area.
4. In KO mice, the degree of myocardial damage was less marked, and the expression of metalloproteinase was smaller than in WT, suggesting the involvement of TNF-α in the pathogenesis after myocardial infarction partly through metalloproteinase. The expression of metalloproteinase in non-infarcted area indicates the involvement of metalloproteinase in the cardiac remodeling. Anti-cylokine therapy on cardiac failure and remodeling may became a useful strategy.
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