2000 Fiscal Year Final Research Report Summary
Regulation of Synthesis and Degradation of Extracellular Matrix in Acute Myocardial Infarction
| Project/Area Number |
11670691
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
MAKINO Naoki Medical Institute of Bioregulation Kyushu Univ. Professors, 生体防御医学研究所, 教授 (60157170)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Shinji Medical Institute of Bioregulation Kyushu Univ.Assistant Professors, 生体防御医学研究所, 講師 (60274445)
YANO Kenichi Medical Institute of Bioregulation Kyushu Univ.Research Associates, 生体防御医学研究所, 助手 (60230281)
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| Project Period (FY) |
1999 – 2000
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| Keywords | myocardial infarction / Extracellular Matrix / Myocardial Fibrosis / Tissue Necrosis Factor / matrix metaloproteinase |
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| Research Abstract |
ABSTRACT
Previous studies suggest that the balance between matrix metalloproteinase (MMPs) and tissue inhibitors of matrix metallotroteinases (TIMP) abundance were important in the setting of dilated cardiomyopathy. The synthesis of MMPs is also regulated by a number of cytokines and growth factors. The present study was undertaken to examine whether tumor necrosis factor-a (TNF-a) preceded in infarcted myocardium in prior to expressions of MMPs and TIMPs and whether those expressions and activations mediate many of the morphological changes that occur after myocardial infarction (MI) at both infarcted and non-infarcted regions. MI was induced by surgical occlusion of the left main coronary artery in rats. Collagen content in infarct zone increased four folds at the first week, while in the non- infarct zone this content increased two folds at the first week. By the RT-PCR method, mRNAs levels for MMP-13 and MMP-2 were both enhanced at day 7 to day 14 and thereafter decreased at day 28. MMP-3 and MMP-14 mRNA expressions were more expressed at day 14 and 28 after MI.MMP-9 mRNA expression also increased from day 1 to day 7. The levels of TIMP-1 and TIMP-2 mRNA expressions were elevated within 1 week and thereafter reduced. TIMP-3 mRNA was more expressed from day 14. TNF-a mRNA in the infarct zone increased from day 2 to day 7 although those levels were still elevated to day 28. The maximal TNF-a protein levels (7-fold increase) were day 7 in the infarct zone. Thus, MMP-9 (neutrophil gelatinase) was co-expressed with TNF-a at early phase after MI and other MMPs and TIMPs were then expressed within one week. Immunohistochemical study in infarct zone was also evaluated as seen in results of gene and protein expressions. Present results therefore suggest that TNF-a secreted from neutrophils in infarct zone after MI may precede in infarcted myocardium in prior to the expression of other matrix degradative enzymes.
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Research Products
(10 results)
