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Role of Cardiac Specific Renin-Angiotensin Sytem in Cardiac Hypertrophy-Studies on Transgenic Mouse

Research Project

Project/Area Number 06404033
Research Category

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

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionHokkaido University

Principal Investigator

KITABATAKE Akira  Hokkaido University Medicine, Professor, 医学部, 教授 (00124769)

Co-Investigator(Kenkyū-buntansha) OIKAWA Tuneyuki  Sasaki Institute, Director, 細胞遺伝部, 部長 (80150241)
OKAMOTO Hiroshi  Hokkaido University Hospital, Assistant Professor, 医学部・附属病院, 助手 (50260394)
KAWAGUCHI Hideaki  Hokkaido University Medicine, Professor, 医学部, 教授 (70161297)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥21,000,000 (Direct Cost: ¥21,000,000)
Fiscal Year 1995: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1994: ¥17,100,000 (Direct Cost: ¥17,100,000)
Keywordscardiac hypertrophy / renin-angiotensin system / transgenic mouse / heart failure / gene polymorphism / cardiomyopathic hamster / angiotensinogen / angiotensin-converting enzyme / 遺伝子 / 組織レニン、アンジオテンシン系 / 心筋肥大 / transgenic mouse / レニン / アンジオテンシン / パラクライン・オートクライン機構
Research Abstract

The aim of this research project was to establish the transgenic mouse, which would be made by transfer renin-angiotensin system genes with cardiac specific promotor to mouse oocytes to clarify the tissue-apecific role of genes of renin-angiotensin system in hte mechanism of cardiac hypertrophy. We have demonstrated that hypertrophic cardiomyopathy (HCM), especially in sporadic cases, is partially determined by genetic disposition and the molecular variant of angiotensin-converting enzyme D allele and angiotensinogen T235 seems to be a predisposing factor for cardiac hypertrophy. We have reported that in the experimental models of cardiac hypertrophy, gene expressions for renin, angiotensinogen, and angiotensin-converting enzyme were enhanced and signals leading to hypertrophy were processing through angiotensin type1 receptor and Gq coupling inositol phosphatide metabolism. We also obtained cardiac-specific promotor region of myosin to express the transfected gene within the heart. We have developed an adenovirus mediated gene transfer system, in which angiotensin-converting enzyme gene can easily transfected in vivo. Although ther remain several steps to be overcome before making transgenic animal models of the renin-angiotensin system, these sophisticated studies provide original and important findings in the field of molecular cardiology.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Mochizuki-Endo U.et al: "Expression of Renin and Angiotensin-Converting Enzyme in Human Hearts" Heart & Vessels. 10. 285-293 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawaguchi H.et al: "Phosphatydilinositol and Inositol Phosphatide Metabolism in Hypertrophic Rat Heart" Progress in Hypertension. 139-157 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoneya K.et al: "Angiotensin-Converting Enzyme Gene Polymorphismin Japanese Patients with Hypertrophic Cardiomyopathy" Am Heart J. 130. 1089-1093 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okadka H.et al: "Alteration of Extrace Ilular Matrix in Dilated Cardiomyopathic Hamster Heart" Moll Cell Biochem. 156. 9-5 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watano K.et al: "Neuro fibromatosis Complicated with XXX Syndrome and Renovascular Hypertension" J.Intern Med.239. 531-535 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishanov A.et al: "Angiotensinogen Gene Polymorphism in Japanese Patients With Hypertrophic Cardiomyopathy" Am Heart J. 133. 184-189 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawaguchi H.et al: "Heart Hyper trophy and Failure" Dhall.NS,Rerce GN et al., 473 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Endo-Mochizuki Y,Mochizuki N,Sawa H,Takada A,Okamoto H,Kawaguchi H,Nagashima K,Kitabatake A: "Expression of renin and angiotensin-converting enzyme in human hearts." Heart and Vessels. 10. 285-293 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawaguchi H,Akira Kitabatake: "Phosphatydilinositol and Inositol Phosphatide Metabolism in Hypertrophic Rat Heart" Progress in Hypertension. 139-157 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoneya K,Okamoto H,Machida M,Onozuka H,Noguchi M,Mikami T,Kawaguchi H,Murakami M,Uede T,Kitabatake A: "Angiotensin-Conveting Enzyme Gene Polymorphism in Japanese Patients With Hypertrophic Cardiomyopathy." Am Heart J. 130. 1089-1093 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Okada H,Kawaguchi H,Kudo T,Sawa H,Okamoto H,Watanabe S,Urasawa K,Murakami T,Kitabatake A: "Alteration of extracellular matrix in dilated cardiomyopathic hamster heart." Mol Cell Biochem. 156. 9-15 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watano K,Okamoto H,Chika Takagi, Hisashi Matsuo H,Hirao N and Akira Kitabatake A: "Neurofibromatosis Complicated with XXX Syndrome and Renovascular Hypertension." J Internal Med. 239. 531-535 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishanov A,Okamoto H,Yoneya K,Watanabe M,Nakagawa I,Onozuka H,Mikami T,Kawaguchi H,Hata A,Kondo K,Kitabatake A.: "Angiotensinogen Gene polymorphism in Japanese patients with Hypertrophic cardiomyopathy." Am Heart J Machida M. 133. 184-189 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideaki Kawaguchi, Akira Kitabateke: Heart Hypertrophy and Failure.Dhalla NS et., 473 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoneya K: "Angiotensin-converting enzyme gene polymorphyism in Japanese patients with hypertrophic cardiomyopathy." Am Heart J. 130. 1089-1093 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Endo-Mochizuki Y: "Expression of renin and angiotensin-converting enzyme in human hearts." Heart and Vessels. 10. 285-293 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okada H: "Alteration of extracellular matrix in dilated cardiomyopathic hamster heart." Mol Cell Biochem,. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Watano K: "Neurofibromatosis Complicated with XXX Syndrome and Renovascular Hypertension" J of Internal Medicine. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kawaguchi H: "Heart hypertrophy and failure(The alteration of signal transduction system in heart failure.)" 463-473. (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroshi Okamoto: "Microdynamics of the phospholipid bilayer in cardiomyopathic hamster heart cell membrane" J Mol Cell Cardiol. 26. 211-218 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kenji Iizuka: "Tranforming Growth Factor beta-1 Modulates the number of Beta Adrenergic Receptor in Cardiac Fibroblasts" J Mole Cell Cardiol. 26. 435-440 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hirofumi Sawa: "Distribution of angiotensinogen in diseased human hearts" Mol Cell Biochem. 132. 15-23 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shinnosuke Muramoto: "Cytosolic localization of β 3-subunit of heterotimeric GTP binding protein in rat hearts" Biochem Biophys Res Commun. 206. 799-804 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hideaki Kawaguchi: "Renin・angiotensin system in heart failure" J Mole Cell Cardiol. 27. 201-209 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hideaki Kawaguchi: "The Cardiomyopathic heart" M.Nagano and N.S.Dhalla, 464 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hideaki Kawaguchi: "The adapted heart" M.Nagano、N.Takeda and N.S.Dhalla, 520 (994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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