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Clinical implication of cardiovascular hormones

Research Project

Project/Area Number 10307026
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NAKAO Kazuwa  Kyoto Univ., Med. and Clin. Sci., Professor, 医学研究科, 教授 (00172263)

Co-Investigator(Kenkyū-buntansha) MUKOYAMA Masashi  Kyoto Univ., Med. and Clin. Sci., Assistant Professor, 医学研究科, 助手 (40270558)
ITOH Hiroshi  Kyoto Univ., Med. and Clin. Sci., Associate Professor, 医学研究科, 講師 (40252457)
SAITO Yoshihiko  Kyoto Univ., Med. and Clin. Sci., Associate Professor, 医学研究科, 助教授 (30250260)
OGAWA Yoshihiro  Kyoto Univ., Med. and Clin. Sci., Assistant Professor, 医学研究科, 助手 (70291424)
田中 一成  京都大学, 医学研究科, 助教授 (80179738)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥38,800,000 (Direct Cost: ¥38,800,000)
Fiscal Year 2000: ¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 1999: ¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 1998: ¥22,000,000 (Direct Cost: ¥22,000,000)
KeywordsCT-1 / BNP / CNP / knockout mice / cultured myocytes / cardiac fibrosis / endochondral ossification / C型ナトリウム利尿ペプチド / 局所調節因子 / 成長板軟骨 / トランスジェニックマウス / 脳性ナトリウム利尿ペプチド / 心臓ホルモン / アンジオテンシン変換酵素 / 心室圧負荷モデル / ANP / GC-A / GC-B / トランスジェニック
Research Abstract

We previously reported that, using in vivo myocytes-nonmyocytes co-culture model, endothelin-1 secreted from nonmyocytes are involved in the process of cardiac hypertrophy. In this study, we examined a role of CT-1, a novel interleukin-6 related cytokine having ability to evoke cardiac cell hypertrophy, in the myocytes-nonmyocytes interaction in an in vitro model of cardiac hypertrophy. We showed that CT-1 plays a role in the hypertrophic process in the co-culture, suggesting a role of CT-1 as a local regulator during cardiac hypertrophy.
BNP is a cardiac hormonc produced primarily by ventricular myocytes. In this study, we generated mice with targeted disruption of BNP (BNP^<-/-> mice). We observed multifocal fibrotic lesions in the ventriceles from BNP^<-/-> mice. No signs of systemic hypertension and ventricular hypertrophy are noted in BNP^<-/-> mice. In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in BNP^<-/-> mice, whereas no f … More ocal fibrotic changes arc found in wild-type littermates. This study establishes BNP as a cardiomyocyte-derived antifibrotic factor in vivo and provides cvidence for its role as a local regulator of ventricular remodeling.
CNP occurs in a variety of central and peripheral tissues, where it acts as an autocrine and paracrinre regulator. In this study, we generated mice with targeted disruption of CNP(CNP^<-/-> mice).The CNP^<-/-> mice show severe dwarfism as a result of imparired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal developmcnt. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of CNP^<-/-> micc and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapcutic implication in some forms of skeletal dysplasia. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] H.Chusho et al.: "Dwarfism and early death in mice lacking C-type natriuretic peptide."Proc.Natl.Acad.Sci.USA. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Kuwahara et al.: "Neuron-restrictive silencer element/neuron-restrictive silencer factor system regulates basal and endothelin-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(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Yamashita et al.: "Flkl-positive cells derived from embryonic stem cells serve as vasculai progenitors."Nature. 408. 92-96 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Chusho et al.: "Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways."Endocrinology. 141. 3807-3813 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Tamura et al.: "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(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Suda et al.: "Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide."Proc.Natl.Acad.Sci.USA. 95. 2337-2342 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Chusho, N.Tamura, Y.Ogawa, A.Yasoda, M.Suda, T.Miyazawa, K.Nakamura, K.Nakao, T.Kurihara, Y.Komatsu, H.Itoh, K.Tanaka, Y.Saito, M.Katsuki, and K.Nakao: "Dwarfism and early death in mice lacking C-type natriuretic peptide."Proc.Natl.Acad.USA. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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, and K.Nakao: "Neuron-restrictive silencer e1ement/neuron-restrictive silencer factor system regulates basal and endothelin-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
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamashita, H.Itoh, M.Hirashima, M.Ogawa, S.Nishikawa, T.Yurugi, M.Naito, K.Nakao, and S.Nishikawa: "Flkl-positive cells derived from embryonic stem cells serve as vascular progenitors."Nature. 408. 92-96 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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, and K.Nakao: "Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways."Endocrinology. 141. 3807-3813 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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, and 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
    • Related Report
      2000 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Chusho et al.: "Dwarfism and early death in mice lacking C-type natriuretic peptide."Proc.Natl.Acad.Sci.USA. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] J.Yamashita et al.: "Flk1-positive cells derived ffrom embryonic stem cells serve as vascular progenitors."Nature. 408. 92-96 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Kuramoto et al.: "Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system."Proc.Natl.Acad.Sci.USA. 98. 559-564 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Chusho et al.: "Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways."Endocrinology. 141. 3807-3813 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Tamura et al.: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc.Natl.Acad.Sci.USA. 97. 4239-4244 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Kotani et al.: "Multiple signal transduction pathways through two prostaglandin Ereceptor EP3 subtype isoforms expressed in human uterus."J.Clin.Endocrinol.Metab.. 85. 4315-4322 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Naohisa Tamura et al.: "Cardiac fibrosis in mice lacking brain natriuretic peptide"Proc. Natl. Acad. Sci. USA. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masato Kasahara et al.: "Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation"J. Am. Soc. Nephrol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shigeo Yura et al.: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin"J. Clin. Invest. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Megumi Aizawa-Abe et al.: "Pathophysiologic role of leptin in obesity-related hypertension"J. Clin. Invest. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koichiro Kuwahara et al.: "Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocyte interactions during hypertrophy of rat cardiac myocytes in vitro"Circulation. 100. 1116-1124 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中所英樹他: "利尿ペプチドファミリーの役割"血管と内皮. 10・1. 85-92 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Kuwahara et al.: "Involvement of cardiotrophin-1 in cardiac myocyte-nonmyocite interactions during hypertrophy of rat cardiac myocytes in vitro." Cirulation. (in press) (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Suda et al.: "Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide." Proc.Natil.Acad.Sci.USA. 95. 2337-2342 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Suga et al.: "Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages." Endocrinology. 139. 1920-1926 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Yasoda et al.: "Natriuretic peptide regulation of endochondral ossification-Evidence for possible roles of C-type natriuretic peptide-guanylyl cyclase-B pathway." J.Biol.Chem.273. 11695-11700 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Yamashita et al.: "Identification of cis-elements of the human endothelin-A receptor gene and inhibition of the gene expression by the decoy strategy." J.Biol.Chem.273. 15993-15999 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Inoue et al.: "Vascular endothelial growth factor(VEGF)expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis." Circulation. 98. 2108-2116 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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