| Project/Area Number |
13670706
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
KIHARA Yasuki Kyoto Univ., Grad. Sch. Med., Instructor, 医学研究科, 講師 (40214853)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | heart failure / cardiac hypertrophy / ventricular remodeling / metalloproteinase / collagen matrix / salt-sensitive rat / コラーゲン / 細胞間質 / ダール食塩感受性ラット / 遺伝子解析 / Differential Display法 / Signal Sequence Trap法 |
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| Research Abstract |
(1) Dynamic regulation of myocardial tissue matrix by net activations of tissue mettaloproteinases (MMP) and their tissue inhibitors (TIMP) : Using Dahl salt-sensitive hypertension rats with heart failure transition, we compared tissue MMP versus TIMP activations before and after the development of heart failure. Along with heart failure transition, the scanning electron microscope clearly demonstrated the destruction of the thin collagen network that was associated with relative (net) domination of MMP activities.
(2) Exogenous supply of a TIMP inhibits the ventricular remodeling: We chronically treated these animals with ONO-4817, a TIMP-2 inhibitor. With this treatment, the rats survived longer, and their LV function remained normal without the remodeling. Therefore, such an intervention could be an adjuvant therapy for patients encountering the ventricular remodeling.
(3) Upstream regulation of MMP/TIMP in the tissue of failing hearts: Chronic treatment of the animals with ONO-4817 on the top of an angiotensin II receptor blocker, valsaltan, showed the similar survival. Thus, it is conceivable that the RAS may directly regulates the MMP/TIMP activities, and full inhibition of RAS may be enough to suppress the Extracellular matrix degradation and ventricular remodeling.
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