2004 Fiscal Year Final Research Report Summary
Pathophysiological role of adrenomedullin in cardiovascular disease and its clinical application as therapeutic drug and diagnostic test
| 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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| Keywords | adrenomedullin / pericardial fluid / AM-mature / AM-glycine / hypertension / heart failure / CRLR / RAMP |
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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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[Journal Article] Up-regulated synthesis of mature-type adrenomedullin in coronary circulation immediately after reperfusion in patients with anterior acute myocardial infarction.2005
Author(s)
Yasu T, Nishikimi T, Kobayashi N, Ikeda N, Ueba H, Nakamura T, Funayama H, Kubo N, Kawakami M, Matsuoka H, Kangawa K, Saito M
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Alteration of renal adrenomedullin and its receptor system in the severely hypertensive rat : effect of diuretic.2005
Author(s)
Nishikimi T, Wang X, Akimoto K, Tadokoro K, Mori Y, Ishikawa Y, Ishimura K, Yoshihara F, Minamino N, Kangawa K, Matsuoka H
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Journal Title
Regul Pept 124
Pages: 89-98
Description
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[Journal Article] Fasudil, a Rho-kinase inhibitor, attenuates glomerulosclerosis in Dahl salt-sensitive rats.2004
Author(s)
Nishikimi T, Akimoto K, Wang X, Mori Y, Tadokoro K, Ishikawa Y, Shimokawa H, Ono H, Matsuoka H
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Journal Title
J Hypertens 22
Pages: 1787-1796
Description
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[Journal Article] Different secretion patterns of two molecular forms of cardiac adrenomedullin in pressure- and volume-overloaded human heart failure.2004
Author(s)
Nishikimi T, Asakawa H, Iida H, Matsushita Y, Shibasaki I, Tadokoro K, Mori Y, Mori H, Mochizuki Y, Okamura Y, Miyoshi S, Kangawa K, Matsuoka H
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Journal Title
J Card Fail 10
Pages: 321-327
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Gene expression, secretion, and autocrine action of C-type natriuretic peptide in cultured adult rat cardiac fibroblasts.2003
Author(s)
Horio T, Tokudome T, Maki T, Yoshihara F, Suga S, Nishikimi T, Kojima M, Kawano Y, Kangawa K
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Journal Title
Endocrinology 144
Pages: 2279-2284
Description
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[Journal Article] Two molecular forms of adrenomedullin in congenital heart disease.2003
Author(s)
Watanabe K, Nishikimi T, Takamuro M, Yasuda K, Ishikawa Y, Tanabe S, Yamada O, Nagaya N, Matsuoka H, Kangawa K, Echigo S
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Journal Title
Pediatr Cardiol 24
Pages: 559-565
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular forms of adrenomedullin in pericardial fluid and plasma in patients with ischaemic heart disease.2002
Author(s)
Nishikimi T, Shibasaki I, Iida H, Asakawa H, Matsushita Y, Mori H, Mochizuki Y, Okamura Y, Horinaka S, Kangawa K, Shimada K, Matsuoka H
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Journal Title
Clin Sci 102
Pages: 669-677
Description
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