2000 Fiscal Year Final Research Report Summary
Cardio-Protective actions of the natriuretic peptide system
| Project/Area Number |
11838020
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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 Institution | Research Institute for Production Development |
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Principal Investigator |
KISHIMOTO Ichiro Research Institute for Production Development, Research Fellow, 成人病科学研究室, 研究員 (80312221)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Yoshihiko Kyoto University, Department of Medicine and Clinical Science, Associate Professor, 医学研究科, 助教授 (30250260)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Guanylyl Cyclase-A / Atrial Natriuretic Peptide / Brain Natriuretic Peptide / Cardiac Hypertrophy / Angiotensin Recepter / Cardiac Fibrosis |
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| Research Abstract |
The mice deficient for guanylyl cyclase (GC)-A, a receptor for natriuretic peptides, display marked cardiac hypertrophy and interstitial fibrosis. In the present study, we examined the mechanism of the hypertrophy and exaggerated fibrosis in GC-A knock out (KO) mice. Since the renin-angiotensin system plays an important role for the establishment of cardiac hypertrophy and fibrosis, we studied the effect of angiotensin II type I receptor (AT1R) antagonist on the heart of GC-A KO.Treatment of GC-A KO with AT1R antagonist dramatically reduced cardiac hypertrophy and fibrosis. Treatment with hydralazine or 6-OHDA decreased blood pressure but these agents did not reduce cardiac hypertrophy. There were marked increases in TGF-b, collagen I and collagen III mRNA expression in the heart of GC-A KO and the augmented gene expressions were also decreased in AT1R antagonist-treated mice To confirm the above results, we next established the mice deficient for both GC-A and AT1R which showed similar reductions in cardiac hypertrophy and fibrosis. Taken together, these results suggested that the natriuretic peptide-GC-A pathway has inhibitory actions on the exaggerated angiotensin system. Therefore, the endogenous natriuretic peptide-GC-A pathway acts in a cardioprotective manner.
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[Publications] I.Hamanaka, Y.Saito, H.Yasukawa, I.Kishimoto, K.Kuwahara, Y.Miyamoto, M.Harada, E.Ogawa, N.Kajiyama, N.Takahashi, T.Izumi, R.Kawakami, I.Masuda, A.Yoshimura, K.Nakao.: "Induction of JAB/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3 Is Involvedin gp130 Resistance in Cardiovascular System in Rat Treated with Cardiotrophin-1 (CT-1) in vivo."Circ.Res.. 88. 727-732 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] K.Kuwahara, Y.Saito, E.Ogawa, N.Takahashi, Y.Nakagawa, Y.Naruse, M.Harada, I.Hamanaka, T.Izumi, Y.Miyamoto, I.Kishimoto, R.Kawakami, M.Nakanishi, N.Mori, K.Nakao.: "Neuron-Restrictive Silencer Element/Neuron-Restrictive Silencer Factor System Regulates Basal-and Endothe lin-1-Inducible Atrial Natriuretic Peptide Gene Expression in Ventricular Myocytes"Mol Cell Biol. 21. 2085-2097 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] H.Chusho, Y.Ogawa, N.Tamura, M.Suda, A.Yasoda, T.Miyazawa, I.Kishimoto, Y.Komatsu, H.Itoh, K.Tanaka, Y.Saito, D.L.Garbers, K.Nakao.: "Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways."Endoerinology. 141. 3807-3813 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Y.Miyamoto, Y.Saiko, M.Nakayama, Y.Shimasaki, T.Yoshimura, M.Yoshimura, M.Harada, N.Kajiyama, I.Kishimoto, K.Kuwahara, J.Hino, E.Ogawa, I.Hamanaka, S.Kamitani, N.Takahashi, R.Kawakami, K.Kangawa, H.Yasue, K.Nakao.: "Replication protein A1 reduces transcription of the endothelial nitricoxide synthase gene containing a T-786→C mutation associated with coronary spastic angina."Hum.Mol.Genet.. 9. 2629-2637 (2000)
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「研究成果報告書概要(欧文)」より
