1998 Fiscal Year Final Research Report Summary
Significance of interaction between myocytes and non-myocytes in ventricular hypertrophy.
| Project/Area Number |
09470168
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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 University |
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Principal Investigator |
SAITO Yoshihiko Kyoto Univ., Grad.Sc.of Med., Assistant Professor, 医学研究科, 助手 (30250260)
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| Co-Investigator(Kenkyū-buntansha) |
HOSODA Kiminori Kyoto Univ., Grad.Sc.of Human and Environmental Studies, Assistant Professor, 人間環境学研究科, 助手 (40271598)
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| Project Period (FY) |
1997 – 1998
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| Keywords | endothelin-1 / cardiotrophin-1 / fibronectin / myocyte hypertrophy |
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| Research Abstract |
Growing evidence indicates that the interaction of myocyte (MC) and non-MC .(NMC) occurs in the remodeling of ventricular hypertrophy. We have developed the pure MC culture and MC-NMC co-culture system to examine the involvement of endothelin-1 (ET-1), cardiotrophin-1 (CT-i) and extracellular matrix proteins, fibronectin (Fin) in the interaction.
ET-1 and CT-i mRNA were expressed mainly in NMC and much less expressed in MC.The substantial amount of ET-l and CT-i were also detected in the culture medium of the NMC culture. When MCs were co-cultured with NMC, MCs induce hypertrophic responses, such as ANP/BNP production, the increase in cell size and augmentation of protein synthesis. ETA receptor antagonist or anti-CT-1 antibody significantly suppressed the hypertrophic response in the co-culture, and the effect of BQ1 23 and anti CT-i Ab was additive in nature. These findings clearly indicate that ET-1 and CT-i are paracrine hypertrophic factors mainly secreted from NMC.We also examined the effect of Fn on MC.Fn-coating dose-dependently increased protein synthesis and ANP/BNP secretion, accompanied by FAK phosphorylation. The RGD peptide suppressed the Fin-induced hypertrophied response of MC on the pure MC and the hypertrophic response observed in the co-culture, suggesting that Fn is not merely passive participant but an active molecute in the MC hypertrophy. The present study indicates important roles of the MC-NMC interaction in the ventricular remodeling via paracrine factors and extracellular matrix proteins.
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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.: "A T-786 C mutation in the endothelial nitric oxide synthase gene is associated with coronary apasm : reduction in pomorter activity." Circulation. (in press). (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.Oagawa, Y.Miyamoto, I.Hamanaka, S.Kamitani, N.Kajiyama, N.Takahashi, O.Nakagawa, I.Masuda, K.Nakao: "Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocyte interactions during hypertrophy of rat cardiac myocytes in vitro." Circulation.(in press). (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Y.Shimasaki, Y.Hirofumi, Y.Michihiro, M.Nakayama, K.Kugiyama, H.Ogawa, E.Harada, T.Masuda, W.Koyama, Y.Saito, Y.Miyamoto, Y.Ogawa, K.Nakao.: "Association of the Missense Glu 298 Asp Mutation of the Endothelial Nitric Oxide Synthase Gene with Myocardial Infarction." J.Am.Coll.Cardiol.31. 1506-1510 (1998)
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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.Saito, N.Kajiyama, M.Yoshimura, Y.Shimasaki, M.Nakayama, S.Kamitani, M.Harada, M.Ishikawa, K.Kuwahara, E.Ogawa, I.Hamanaka, N.Takahashi, T.Kaneshige, H.i Teraoka, T.Akamizu, N.Azuma, Y.Yoshimasa, T.Yoshimasa, H.Itoh, I.Masuda, H.Yasue, K.Nakao.: "Endothelial Nitric Oxide Synthase Gene is Positively Associated With Essential Hypertension." Hypertension.32. 3-8 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] M.Suda, Y.Ogawa, K.Tanaka, N.Tamura, A.Yasoda, T.Takigawa, M.Uehira, H.Nishimoto, H.Itoh, Y.Saito, K.Shiota, and K.Nakao.: "Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide." Proc.Natl.Acad.Sci.USA.95. 2337-2342 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] M.Harada, H.Itoh, O.Nakagawa, Y.Ogawa, Y.Miyamoto, K.Kuwahara, E.Ogawa, T.Igaki, J.Yamashita, I.Masuda, T.Yoshimasa, I.Tanaka, Y.Saito, K.Nakao.: "Significance of Ventricular Myocytes and Nonmyocytes Interaction During Cardiocyte Hytertrophy.-Evidence for Endothelin-1 as a Paracrine Hypertrophic Factor from Cardiac Nonmyocytes-." Circulation.96. 3737-3744 (1997)
Description
「研究成果報告書概要(欧文)」より
