Roles of mast cells, stem cell factor and c-kit in heart failure
| Project/Area Number |
16390223
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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 | Kyoto University |
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Principal Investigator |
MATSUMORI Akira Kyoto University, Department of Cardiovascular Medicine, Associate Professor, 医学研究科, 助教授 (70135573)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIO Ryosuke Kyoto University, Division of Emergency Medicine, Assistant Professor, 医学研究科, 助手 (00335275)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2005: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2004: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | Mast cell / Stem cell factor / heart failure / Myocarditis / c-kit / Mast cell / Myocarditis / Mutant mice |
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| Research Abstract |
Mast cells are powerful producers of multiple cytokines, chemical mediators, and proteases, playing a principal role in the pathogenesis of heart failure. We investigated the roles of mast cells, an essential factor for proliferation and differentiation of mast cells, stem cell factor (SCF) and its receptor c-kit in heart failure in human and an animal model in mice. Number of mast cells, and the expression of SCF are increased in patients with heart failure.
We found that the expression of stem cell factor (SCF), mast cell growth factor, and mast cell density were significantly increased in the heart of murine heart failure model due to encephalomyocarditis virus (EMCV) myocarditis. We showed that using two strains of mast cell deficient mice, the lack of mast cells in the heart protected mice against lethality due to acute EMCV myocarditis, and that the reconstitution of mast cells to their deficient mice deteriorated myocarditis compared with their control mice.
The gene expressions of mast cell proteases were upregulated in the acute phase of viral myocarditis, and rose further in the subacute phase of heart failure. Their activation coincided with the development of myocardial necrosis and fibrosis, and correlated with the upregulation of the gene expressions of mast cell chymase and matrix metalloproteinase (MMP)-9. These findings suggest that mast cells participate in the acute inflammatory reaction and in the beginning of the ventricular remodeling process associated with acute viral myocarditis.
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Report
(3 results)
Research Products
(28 results)
