| Project/Area Number |
15390250
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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 |
Circulatory organs internal medicine
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| Research Institution | University of Miyazaki (2004-2005)
宮崎医科大学 (2003) |
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Principal Investigator |
ETO Tanenao University of Miyazaki, Executive Director, 理事 (10038854)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Kazuo University of Miyazaki, 1st Dept Intern Med, Professor, 医学部, 教授 (50204912)
KATO Johji University of Miyazaki, 1st Dept Intern Med, Research Associate, 医学部, 助手 (20274780)
KITA Toshihiro University of Miyazaki, 1st Dept Intern Med, Research Associate, 医学部, 助手 (70315365)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2005: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | adrenomedullin / CRLR / RAMP / hypertension / acute myocardial infarction / vascular damage / PAMP / colon ulcer / 心血管線維化 / 心肥大 / 大腸炎症 / 血管外膜線維化 / 左室肥大 / 心筋線維化 / 左室リモデリング / 糸球体腎炎 / アミド化酵素 / 中間型AM / CRLR / RAMPs / 食塩負荷 / 受容体特異性 |
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| Research Abstract |
Aim of this study : This research project was planned to characterize the protective actions of adrenomedullin (AM) for the heart and blood vessels in vitro and in vivo in the cardiovascular diseases. Results : 1.Function and expression of the AM receptor proteins of CRLR and RAMPs were found to be up-regulated by angiotensin II in cultured cardiac myocytes. A functional analysis study revealed an intra-molecular portion important for the ligand specificity of human RAMP1. 2.Both AM production and the AM receptor system were up-regulated in various tissues of animal models of salt-loading, hypertension and nephritis. 3.When infused in the early phase of acute myocardial infarction of rats, AM reduced mortality and alleviated progression of left ventricular remodeling and heart failure. 4.AM improved endothelium-dependent vasodilatation and lessened perivascular fibrosis in rat models of hypertension. 5.These cardiovascular protective effects of AM were found to be mediated by a number of mechanisms including inhibitions of oxidative stress and the renin-angiotensin system or suppressions of pro-fibrotic factors and activation of fibroblasts. 6.Transgenic rats over-expressing proadrenomedullin N-terminal 20 peptide (PAMP) showed lesser cardiac hypertrophy and fibrosis induced by volume and salt loading. 7.In rats with acetic acid-induced colitis, ulceration was ameliorated by intra-colonic administration of AM. Conclusion : AM and the AM receptor system were up-regulated in various types of cells and tissues, presumably inhibiting progression of the cardiovascular diseases. AM exerted a wide range of effects protective for the heart and blood vessels through a number of mechanisms, suggesting that this bioactive peptide is beneficial for treatment of the cardiovascular diseases.
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