2005 Fiscal Year Final Research Report Summary
Involvement of NRSF-mediated Transcriptional Silencing System in Molecular Mechanism of Chronic Heart Failure
| Project/Area Number |
16390228
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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 | NARA MEDICAL UNIVERSITY |
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Principal Investigator |
SAITO Yoshihiko Nara Medical University, First Department of Medicine, Professor, 医学部, 教授 (30250260)
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| Co-Investigator(Kenkyū-buntansha) |
UEMURA Shiro Nara Medical University, First Department of Medicine, Associate Professor, 医学部, 講師 (80232792)
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| Project Period (FY) |
2004 – 2005
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| Keywords | NRSF / ANP / BNP / CACNA1H / Goα / heart failure |
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| Research Abstract |
Neuron Restrictive Silencer Factor (NRSF), a strong transcriptional silencer protein, binds Neuron Restrictive Silencer Element (NRSE) that is located in the transcriptional regulating region of a number of cardiac embryonic genes. Transgenic mice overexpressing dominant negative form of NRSF mutant driven by α-MHC (α-MHC-dnNRSF-Tg) showed left ventricular dilation, ventricular dysfunction and fatal ventricular arrhythmia, which resemble dilated cardiomyopathy.
The present study has investigated which genes regulated by NRSF during development of heart failure. According to the cDNA array analyses of the left ventricle of α-MHC-dnNRSF-Tg, several genes are significantly up-regulated in Tg mice compared with normal control mice. Some of them, such as ANP,BNP,Goα,CACNA1H, neurotensin receptor 2, and dopamine receptor type 2, contain NRSE in their 5' franking region or intron. In experimental heart failure model of acute myocardial infarction or transverse aortic band, ANP and BNP genes were upregulated but, other genes listed above were not uniformly altered, suggesting NRSF is not a solely transcriptional regulator in development of heart failure. Transgenic mice overexpressing either Goa or CACNA1H under control of a-MHC showed similar phenotypes to those of wild type mice. Further studies are necessary to elucidate important roles of NRSF in development of heart failure.
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[Journal Article] Cardiac expression of placental growth factor predicts the improvement of chronic phase left ventricular function in patients with acute myocardial infarction.2006
Author(s)
H.Iwama, N.Naya, K.Imagawa, Y.Takemoto, O.Asai, K.Onoue, S.Okayama, S.Somekawa, Y.Kida, Y.Takeda, M.Takaoka, H.Kawata, M.Horii, T.Nakajima, N.Doi, Y.Saito.
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Journal Title
J.Am.Coll.Cardiol. 47
Pages: 1559-1567
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of natriuretic peptide receptor guanylyl cyclase-A in myocardial infarction evaluated using genetically engineered mice2005
Author(s)
M.Nakanishi, Y.Saito, I.Kishimoto, M.Harada, K.Kuwahara, N.Takahashi, R.Kawakami, Y.Nakagawa, K.Tanimoto, S.Yasuno, S.Usami, Y.Li, Y.Adachi, A.Fukamizu, D.L.Garders, K.Nakao
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Journal Title
Hypertension 46
Pages: 441-447
Description
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[Journal Article] Hypertrophic responses to cardiotrophin-1 are not mediated by STAT3, but via a MEK5-ERK5 pathway in cultured cardiomyocytes.2005
Author(s)
N.Takahashi, Y.Saito, K.Kuwahara, M.Harada, K.Tanimoto, Y.Nakagawa, R.Kawakami, M.Nakanishi, S.Yasuno, S.Usami, A.Yoshimura, K.Nakao.
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Journal Title
J.Mol.Cell.Cardiol. 38
Pages: 185-192
Description
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