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Difference in β-adrenergic signaling by the etiologies of heart failure

Research Project

Project/Area Number 09670748
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKeio University

Principal Investigator

YOSHIKAWA Tsutomu  Keio University Dept of Med Assistant Professor, 医学部, 講師 (20174906)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Toshiyuki  Keio University Dept of Med, 医学部, 助手 (20286470)
IWATA Michikado  Keio University Dept of Med, 医学部, 助手 (30276224)
ANZAI Toshihisa  Keio University Dept of Med, 医学部, 助手 (60232089)
MAEKAWA Yuichiro  Keio University Dept of Med, 医学部, 助手 (90296575)
中村 岩男  慶應義塾大学, 医学部, 助手 (60265808)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsβ-adrenergic receptor / cardiomyopathy / myocardial infarction / remodeling / guanine nucleotide binding protein / cardiac hypertrophy / G-protein-coupled receptor kinase / uncoupling / 心不全 / β受容体
Research Abstract

We produced two animal models for heart failure including autoimmune-mediated cardiomyopathy induced by β1-adrenergic receptors as a nonischemic cardiomyopathy in rabbits and myocardial infarction as an ischemic cardiomyopathy in rats. In autoimmune-mediated cardiomyopathy, left ventricle exhibited concentric hypertrophy with myocyte hypertrophy, myofiber disorganization, and interstitial fibrosis. Uncoupling of β-adrenergic receptors was based on increases in inhibitory G-protein and type 5 G-protein-coupled receptor kinase (GRK). These phenomena were prevented by bisoprolol treatment. Immunoglobulin G fraction isolated from this rabbits has an intrinsic agonisitic effect, which was inhibited by inverse agonist, bisoprolol in a dosedependent manner. Thus, in this model, autoantibody produced by autoimmunity appears to produced cardiac hypertrophy and signaling abnormalities through acting as an agonist.
We noted that heart failure was induced through remodeling by 6 weeks after coronary artery occlusion of left anterior descending artery in rats. GRK type 2 and protein kinase C ipsilon (PKCε) isoform were both increased as well as uncoupling of β-adrenergic receptors. Short-tem use of angiotensin II type 1 receptor antagonist inhibited the increases in GRK type 2 and PKCε resulting in a reversal of adrenergic receptor uncoupling. These data suggested that activation in renin-angiotensin system induced uncoupling of β1-adrenergic receptor through intracellular crosstalk, contributing over heart failure in the model.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Iwata M,Yoshikawa T, et al: "Autoimmunity against the second extracellular loop of β-adrenergic receptors induces"Cire Res. (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] Iwata M, et al.: "Autoantibodies against the second extracellular loop of beta-adrenergic receptors predict"J Am Coll Cardiol. 37(2). 418-424 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakamura I, et al: " Presynaptic modulation of the norepinephrine-induced β-adrenergic receptor desensitization phenomenon…"J Cardiac Failure. 6(4). 350-358 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi T, et al.: "Absence of preinfarction angina is associated with a risk of no-reflow phenomenon after……"Int J Cardiol. 75. 253-260 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikawa T, et al.: "Effectiveness of carvedilol alone versus carvedilol+pimobendan for cereve heart failure."Am J Cardiol. 85(12). 1495-1497 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Baba A, et al.: "Isoform-specific alterations in cardiac…"J Cardiac Failure. 4(4). 333-341 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 吉川勉: "β遮断薬の全てpart 1.β遮断薬のプロファイル 2.β受容体を介する情報伝達"先端医学社. 24-30 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iwata M, Yoshikawa T, Baba A, et al: "Autoimmunity against the second extracellular loop of β1-adrenergic receptors induces β-adrenergic receptor desensitization and myocardial hypertrophy in vivo."Circ Res. (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] Iwata M, Yoshikawa T, Baba A, et al: "Autoantibodies against the second extracellular loop of beta-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy."J Am Coll Cardiol. 37. 418-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakamura I, Yoshikawa T, Anzai T, et al: "Presynaptic modulation of the norepinephrine-induced β-adrenergic receptor desensitization in vivo"J Cardiac Failure. 6. 350-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi T, Anzai T, Yoshikawa T, et al: "Absence of preinfarction angina is associated with a risk of noreflow phenomenon after primary coronary angioplasty for a first anterior wall acute myocardial infarction."Int J Cardiol. 75. 253-60 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikawa T, Baba A, Suzuki M, et al: "Effectiveness of carvedilol alone versus carvedilol+pimobendan for severe congestive heart failure."Am J Cardiol. 85. 1495-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Baba A, Yoshikawa T, Nakamura I, et al: "Isform-specific alterations cardiac and erythrocyte Na^+, K^+-ATPase activity induced by norepinephrine."J Cardiac Failure. 4. 333-41 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iwata M,Yoshikawa T,Baba A, et al.: "Autoimmunity against the second extracellular loop of β1-adrenergic receptors induces β-adrenergic receptor desensitization and myocardial hypertrophy in vivo."Circ Res. (In press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwata M,Yoshikawa T,Baba A, et al.: "Autoantibodies against the second extracellular loop of beta-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy."J Am Coll Cardiol. 37(2). 418-424 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura I,Yoshikawa T,Anzai T, et al.: "Presynaptic modulation of the norepinephrine-induced β-adrenergic receptor desensitization phenomenon in vivo."J Cardiac Failure. 6(4). 350-358 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi T,Anzai T,Yoshikawa T, et al.: "Absence of preinfarction angina is associated with a risk of no-reflow phenomenon after primary coronary angioplasty for a first anterior wall acute myocardial infarction."Int J Cardiol. 75. 253-260 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshikawa T,Baba A,Suzuki M, et al.: "Effectiveness of carvedilol alone versus carvedilol + pimobendan for severe congestive heart failure."Am J Cardiol. 85(12). 1495-1497 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Baba A,Yoshikawa T,Nakamura I, et al.: "Isoform-specific alterations in cardiac and erythrocyte Naπ, K+-ATPase activity induced by norepinephrine."J Cardiac Failure. 4(4). 333-341 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉川勉: "β遮断薬の全てpart I.β遮断薬のプロファイル 2.β受容体を介する情報伝達"先端医学社. 24-30 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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