Roles of chymase in the development of cardiac remodeling during heart failure progression.
| Project/Area Number |
15590240
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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 |
General pharmacology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
JIN Denan Osaka Medical College, Faculty of Medicine, Assistant Professor, 医学部, 講師 (90319533)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAI Shinji Osaka Medical College, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80288703)
MURAMATSU Michiko Osaka Medical College, Faculty of Medicine, Research Associate, 医学部, 助手 (30330096)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | chymase / angiotensrn II / TGF-β1 / cardiac fibrosis / hepatic fibrosis / 心不全 / 精製 / 心筋症 / シャント |
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| Research Abstract |
It is well known that the mast cell derived chymase plays an important role in the generation of angiotensin (Ang) II form Ang II. In addition to its Ang II generation property, the recent studies confirmed that chymase also participate in the cleavage of latent transforming growth factor-beta 1 (TGF-ss1) to the active forms. Taking together, these results indicating that chymae may act as a fibrogenic facilitating factor to promote various organs remodeling during pathological conditions. To verify our this hypothesis, we have purified chymase from dog tongue, and injected it into the rat liver. In comparison with saline injection, the fibrotic area was significantly large after injection of the purified dog chymase and the fibrotic area was almost reduced to the saline injected level when the chymase was heated at 100 ℃ for 5 minutes. Interestingly, we found that the fibrogenic effect of chymase injection was concentration- and time-dependent. These findings direct demonstrated that
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the increase of chymase indeed accelerating fibrogenic processes, although it was unclear which pathway will be more important during these processes between Ang II-generating property and latent TGF-aa1 activation after injection of the chymase. To further confirm this issue, the effects of a chymase inhibitor and an Ang II receptor antagonist as well as a chymase inhibitor combined with an Ang II receptor antagonist are ongoing in the same model.
The roles of chymase during the development of cardiac hypertrophy and cardiomyopathy were also determined in a hamster model of abdominal arteriovenous (AV) fistula and by employing spontaneous cardiomyopathy hamsters. In these models, our immunohistochemical studies reviewed that the great deposition of chymase positive mast cells always accompanied the significant focal fibrotic legion, and the enzymetic activities of chymase in the disordered hearts were also increased significantly when these compared to the age-matched control normal heats. The effects of chymase inhibition and Ang II blockade as well as their combination to be pronounced in the near future. Less
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(3 results)
Research Products
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