| Project/Area Number |
14570692
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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 | Dokkyo Medical University |
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Principal Investigator |
NISHIKIMI Toshio Dokkyo University, School of Medicine, Associate Professor, 医学部, 助教授 (80291946)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Hiroaki Dokkyo University, School of Medicine, Professor, 医学部, 教授 (20111544)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | adrenomedullin / pericardial fluid / AM-mature / AM-glycine / hypertension / heart failure / CRLR / RAMP / 受容体 / 心肥大 / 腎不全 / アドレノメデュリン受容体 / アミド化酵素 / 心保護作用 / 腎保護作用 / 急性冠症候群 / 褐色細胞腫 |
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| Research Abstract |
1.We demonstrated that long-term administration of adrenomedullin(AM) has renoprotective effects in hypertensive rat model. We also showed putative its mechanism.
2.We investigated the molecular form of AM in the pericardial fluid in ischemic heart disease and heart failure. We showed that AM-mature is higher in pericardial fluid than plasma, and that it is increased in acute coronary syndrome and heart failure induced by pressure overload.
3.To investigate the source of plasma AM in pheochromocytoma patient, we measured plasma AM levels in the plasma obtained from adrenal vein. AM levels in adrenal vein is similar to the AM in other portion, suggesting that AM is produced in the peripheral vascular bed.
4.We investigated the molecular form of AM, mRNA levels of AM,CRLR,RAMP2,and RAMP3 in the cardiac hypertrophy and heart failure, and showed that they are increased in cardiac hypertrophy and further increased in heart failure.
5.We demonstrated that long-term administration of AM delay the progression of heart failure and it improved heart weight, hemodynamics, cardiac function, and cardiac gene expression.
6.We demonstrated that both molecular forms of AM are increased in congenital heart disease and that it is related to hypoxia.
7.We demonstrated that cultured cardiac fibroblasts secrete AM-mature and that cytokine stimulates the production of AM, and mRNA levels of AM,CRLR,RAMP2,and RAMP3. We also showed that endogenous AM exerts as an anti-fibrotic factor.
8.We demonstrated that natriuretic peptides have anti-atherosclerotic effects in vivo and that CNP is produced in the heart.
9.We demonstrated that the deficiency or the reduction of natriuretic peptide receptor gene have susceptibility in heart failure.
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