2000 Fiscal Year Final Research Report Summary
Elucidation of Molecuolar Mechanism for Cardioprotection-Study from Genetic Engineered Mice
| Project/Area Number |
11470161
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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 | KYOTO UNIVIERSITY |
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Principal Investigator |
SAITO Yoshihiko Kyoto University, Department of Midicine and Cinical Science, Associate Professor, 医学研究科, 助教授 (30250260)
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| Co-Investigator(Kenkyū-buntansha) |
KISHIMOTO Ichiro Research Institute for Production Development Research Fellow, 研究員 (80312221)
HOSODA Kiminori Kyoto University, Assistant, 人間環境学研究科, 助手 (40271598)
OGAWA Yoshihiro Kyoto University, Assistant, 医学研究科, 助手 (70291424)
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| Project Period (FY) |
1999 – 2000
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| Keywords | ANP / BNP / GC-A / knockout mice / membrane metalloprotease / P-selectin / ischemia reperfusion injury |
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| Research Abstract |
Accumulating evidence indicates that the natriuretic peptide system plays roles in cardiac remodeling in chronic stage. In the present study we examined effects of high plasma concentration of BNP in acute remodeling after acute myocardial infarction (AMI) in mice overexpressing BNP in the liver, and also effects of target disruption of the gene encoding GC-A, a common receptor for ANP and BNP in ischemia reperfusion injury.
Experiment 1 using BNP transgenic mice : Mice overexpressing BNP showed low survival rate after permanent occlusion of left coronary artery during first 7 days, compared with wild type mice. High mortality was due to higher incidence of free wall rupture accompanied by more abundant infiltration of polymorphnuclear leucocytes. Expression of membrane metalloprotease 9 mRNA was higher in BNP transgenic mice than wild type mice.
Experiment 2 using mice lacking GC-A gene : AMI remains the leading cause of death in civilized countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury that shares many characteristics with inflammatory responses. Endothelial P-selectin-mediated infitration of neutrophils plays a key role in the "reperfusion injury". However, the mechanism of the P-selectin induction is not known. Here, we show that infarct size after ischemia-reperfusion was significantly smaller in mice lacking guanylyl cyclase (GC)-A, a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration, in coronary endothelial P-selectin expression.
These two experiments provide new roles of ratriuretic peptide system in AMI.
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Research Products
(13 results)
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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)
Description
「研究成果報告書概要(欧文)」より
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[Publications] N.Tamura, Y.Ogawa, H.Chusho, K.Nakamura, K.Nakao, M.Suda, M.Kasahara, R.Hashimoto, G.Katsuura, M.Mukoyama. H.Itoh, Y.Saito, I.Tanaka, H.Otani, M.Katsuki, K.Nakao.: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc.Natl.Acad.Sci.USA. 97. 4239-4244 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] N.Tamura, Y.Ogawa, H.Chusho, K.Nakamura, K.Nakao. M.Suda, M.Kasahara, R.Hashimoto, G.Katsuura, M.Mukoyama. H.Itoh, Y.Saito, I.Tanaka, H.Otani, M.Katsuki, K.Nakao.: "Cardiac fibrosis in mice lacking brain natriuretic peptide."
Description
「研究成果報告書概要(欧文)」より
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[Publications] Y.Miyamoto, Y.Saito, 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 nitric oxide synthase gene containing a T-786→C mutation associated with coronary spastic angina."Hum.Mol.Genet.. 9. 2629-2637 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] M.Nakayama, H.Yasue, M.Yoshimura, Y.Shimasaki, K.Kugiyama, S.Sugiyama, H.Sumida, H.Ogawa, Y.Saito, Y.Ogawa, Y.Miyamoto, K.Nakao.: "T-786→C mutation in the endothelial nitric oxide synthase gene is associated with coronary spasm : reduction in promoter activity."Circulation. 99. 2864-2870 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] K.Kuwahara, Y.Saito, M.Harada, M.Ishikawa, E.Ogawa, Y.Miyamoto, I.Hamanaka, S.Kamitani, N.Kajiyama, N.Takahashi, O.Nakasawa, I.Masuda, K.Nakao: "Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocyte interactions during hypertrophy of rat cardiac myocytes in vitro"Circulation. 100. 1116-1124 (1999)
Description
「研究成果報告書概要(欧文)」より
