2005 Fiscal Year Final Research Report Summary
Mechanisms of Action and Pathophysiological Role of Adrenomedullin in Cardiovascular Diseases
| 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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| Keywords | adrenomedullin / CRLR / RAMP / hypertension / acute myocardial infarction / vascular damage / PAMP / colon ulcer |
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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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[Journal Article] Adrenomedullin in mast cells of abdominal aortic aneurysm.2006
Author(s)
Tsuruda, T., Kato, J., Hatakeyama, K., Yamashita, A., Nakamura, K., Imamura, T., Kitamura, K., Onitsuka, T., Asada, Y, Eto, T.
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Journal Title
Cardiovasc Res (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of CGRP and adrenomedullin receptors.2006
Author(s)
Kuwasako, K., Cao, Y.N., Chu, C.P., Iwatsubo, S., Eto, T., Kitamura, K.
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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] Effect of adrenomedullin administration on acetic acid-induced colitis in rats.2005
Author(s)
Ashizuka, S., Ishikawa, N., Kato, J., Yamaga, J., Inatsu, H., Eto, T., Kitamura, K.
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Journal Title
Peptides. 26
Pages: 2610-2615
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Beyond vasodilation : the antioxidant effect of adrenomedullin in Dahl salt-sensitive rat aorta.2005
Author(s)
Cao, Y.N., Kuwasako, K., Kato, J., Yanagita, T., Tsuruda, T., Kawano, J., Nagoshi, Y, Chen, A.F., Wada, A., Suganuma, T., Eto, T., Kitamura, K.
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Journal Title
Biochem Biophys Res Commun. 332
Pages: 866-872
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Antifibrotic effect of adrenomedullin on coronary adventitia in angiotensin II-induced hypertensive rats.2005
Author(s)
Tsuruda, T., Kato, J., Hatakeyama, K., Masuyama, H., Cao, Y.N., Imamura, T., Kitamura, K., Asada, Y., Eto, T.
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Journal Title
Cardiovasc Res. 65
Pages: 921-929
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Adrenomedullin alleviates not only neointimal formation but also perivascular hyperplasia following arterial injury in rats.2005
Author(s)
Tsuruda, T., Kato, J., Matsui, E., Hatakeyama, K., Masuyama, H., Imamura, T., Kitamura, K., Asada, Y., Eto, T.
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Journal Title
Eur J Pharmacol. 508
Pages: 201-204
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats.2004
Author(s)
Nakamura, R., Kato, J., Kitamura, K., Onitsuka, H., Imamura, T., Cao, Y., Marutsuka, K., Asada, Y, Kangawa, K., Eto, T.
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Journal Title
Circulation. 110
Pages: 426-431
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins.2004
Author(s)
Kuwasako, K., Cao, Y.N., Nagoshi, Y., Tsuruda, T, Kitamura, K., Eto, T.
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Journal Title
Mol Pharmacol. 65
Pages: 207-213
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Chronic salt loading upregulates expression of adrenomedullin and its receptors in adrenal glands and kidneys of the rat.2003
Author(s)
Cao, Y.N., Kitamura, K., Kato, J., Kuwasako, K., Ito, K., Onitsuka, H., Nagoshi, Y., Uemura, T., Kita, T., Eto, T.
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Journal Title
Hypertension. 42
Pages: 369-372
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Angiotensin II modulates gene expression of adrenomedullin receptor components in rat cardiomyocytes.2003
Author(s)
Mishima, K., Kato, J., Kuwasako, K., Imamura, T., Kitamura, K., Eto, T.
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Journal Title
Life Sci. 73
Pages: 1629-1635
Description
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