2005 Fiscal Year Final Research Report Summary
Molecular pharmacological study and development of new treatment by investigating endothelin in cardiovascular diseases.
| Project/Area Number |
15390077
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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 |
General pharmacology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
MIYAUCHI Takashi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor (60222329)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Katsutoshi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor (30012660)
SAKURAI Takeshi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor (60251055)
NISHIKIBE Masaru Banyu Pharmacological Company, Tsukuba Pharmacological Institute, Director
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| Project Period (FY) |
2003 – 2005
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| Keywords | cardiovascular disease / endothelin / transcription / fenofibrate / molecular pharmacology / gene expression / endothelin blocker / endothelin antagonist |
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| Research Abstract |
Cardiovascular diseases is a major cause of death in Japan and Western countries. Cardiac myocytes and vascular endothelial cells produce endothelin (ET)-1, which increases the contractility of cardiac muscles and of vascular smooth muscles. ET-1 also exerts long-term effects such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes. In the present work, we studied pathophysiological roles of ET-1 in cardiovascular diseases using molecular biological, biochemical and pharmacological methods. Furthermore, we studied the effects of ET receptor antagonists on the animals with cardiovascular diseases. In the cardiovascular diseases, the production of ET-1 (both mRNA and peptide levels) was markedly increased in the cardiovascular tissues and the long-term treatment with an ET receptor antagonist greatly improved the survival rate of animals with cardiovascular diseases. This beneficial effect was accompanied by amelioration of cardiac dysfunction and amelioration of expression of cardiac genes of molecular markers (ANP mRNA, β-myosin heavy chain mRNA) for cardiovascular diseases. The present study suggests that endogenous ET-1 is involved in the progression of cardiovascular diseases, and that an ET receptor antagonist becomes a new drug for varios cardiovascular diseases.
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