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Myocardial injury due to G-protein-coupled receptor-autoimmunity

Research Project

Project/Area Number 10670679
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKANAZAWA MEDICAL UNIVERSITY

Principal Investigator

MATSUI Shinobu  Medical Research Institute, KANAZAWA MEDICAL UNIVERSITY Professor, 総合医学研究所, 教授 (00064600)

Co-Investigator(Kenkyū-buntansha) TERAOKA Kouhei  Medical Research Institute, KANAZAWA MEDICAL UNIVERSITY Lecturer, 総合医学研究所, 講師 (10102063)
HAYASE Mituru  Department of Clinical Pathology, KANAZAWA MEDICAL UNIVERSITY Lecturer, 医学部, 講師 (90064592)
KATSUDA Syougo  Department of Pathology, KANAZAWA MEDICAL UNIVERSITY Professor, 医学部, 教授 (40110613)
YAMAGUCHI Nobuo  Department of Serology, KANAZAWA MEDICAL UNIVERSITY Professor, 医学部, 教授 (10106916)
KURIHARA Takayuki  Medical Research Institute, KANAZAWA MEDICAL UNIVERSITY Lecturer, 総合医学研究所, 講師 (20064595)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsDilated cardiomyopathy / autoantibody / Synthesized peptide / β1-adrenoceptor / Muscarinic-2 receptor / Autoimmune disease / 自己免疫疾患 / 抗体吸着療法 / 心筋膜受容体 / 自己免疫 / 受容体拮抗薬 / 受容体遮断薬 / 心筋症 / アンギオテンシン変換酵素阻害薬 / 心筋保護
Research Abstract

One of the main mechanisms for dilated cardiomyopathy is likely to be autoimmune mediated myocardial damage. So far, a variety of autoantibodies have been detected against a number of putative autoantigen in the sera of patients with dilated cardiomyopathy. A growing body of studies have conformed that autoantibodies against the second extracellular loop of β1-adrenoceptor and M2-muscarinic receptor are present in 30-40% of patients with dilated cardiomyopathy. These anti-β1 adrenoceptor and anti-M2 muscarinic receptor antibodies can not only decrease the binding sites of antagonist but also recognize the target receptors. Moreover, these two autoantibodies posesses an 'agonist-like' effects on the target receptors. In order to elucidate whether the autoantibodies against these autoimmune epitopes play an important role in pathogenesis of dilated cardiomyopathy, we immunized rabbits over a period of one wear with synthetic peptides corresponding to the second extracellular loop of the β1-adrenoceptor (β1-peptide) and the M2-muscarinic receptor (M2-peptide). These peptides induced morphological changes in the heart similar to those found in dilated cardiomyopathy. From immunohistochemical study of myocardial disorders, antibody-dependent cell-mediated cytotoxity, T-cell mediated cytotoxity and antibody-mediated cellular dysfunction could be the main mechanisms of cardiomyopathic changes in immunized rabbits. β1-adrenoceptor blockade and M2-muscarinic receptor antagonist protected the myocardium from injury induced by each peptide. These clinical and experimental findings suggest that these receptor autoantigens are of pathogenic importance in the development of dilated cardiomyopathy in vivo.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Wallukat G: "Autoantibodies against M2 muscarinic receptors in patients with cardiomyopathy display non-desensitized agonist-like effects"Life Sci.. 64・6/7. 465-469 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayase M: "Immune mechanism of myocardial injurv due to anti- β1-adrenoceptor autoantibody : immunohistological study of myocardial disorders"J.Cardiovasc.Pharmacol.. 34. S29-S32 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsui S: "Active immunization of combined β1-adrenoceptor nd,M2-muscarinic receptor peptides induces cardiac hypertropy in rabbits"J. Card. Fail.. 5(3). 246-254 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsui S: "Protective effect of bisoprolol.on β1-adrenoceptor peptide-induced autoimmune myocardial damage in rabbits."Herz. 25. 267-270 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsui S: "Beneficial effect of angiotensin-converting enzyme inhibitor on dilated cardiomyopathy induced by autoimmune mechanism against β1-adrenoceptor."J. Cardiovasc. Pharmacol.. 36. S43-S48 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zong Z: "Growth hormone interferes with the progression of myocarditis in rats."Eur.J.Pharmacol. (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] 松井忍: "心筋症"メディカルビュー社. 4 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wallukat G et al.: "Autoantibodies against M2-muscarinic receptors in patients with cardiomyopathy display non-desensitized agonist-like effects."Life Sci. 64. 465-469 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hayase M et al.: "Immune mechanism of myocardial injury due to anti-β1-adrenoceptor antibody : immunohistochemical study of myocardial disorders."J Cardiovasc Pharmacol. 34. S29-S32 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsui S et al.: "Active immunization of combined β1-adrenoceptor and M2-muscarinic receptor peptides induces cardiac hypertrophy in rabbits."J Card Fail. 5. 246-254 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsui S et al.: "Protective effect of bisoprolol on β1-adrenoceptor peptide-induced autoimmune myocardial damage in rabbits."Herz. 25. 267-270 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsui S etal.: "Beneficial effect of angiotensin-converting enzyme on dilated cardiomyopathy induced by autoimmune mechanism against β1-adrenoceptor."J Cardiovasc Pharmacol. 36. S43-S48 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zong Z et al.: "Growth hormone interferes with the progression of myocarditis in rat."Eur J Pharmacol. (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] Zong Z: "Growth hormone interferes with the progression of myocarditis in rats."Eur.J.Pharmacol. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsui S: "Beneficia1 effect of angiotensin-converting enzyme inhibitor on dilated cardiomyopathy induced by autoimmune mechanism against β 1-adrenoceptor."J.Cardiovasc.Pharmacol. 36. S43-S48 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsui S: "Protective effect of bisoprolol on β 1-adrenoceptor peptide-induced autoimmune myocardial damaze in rabbits."Herz. 25. 267-270 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 松井忍: "心筋症"メディカルビュー社. 4 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Gerd Wallkat: "Autoantibodies Against M2 Muscarinic Receptors in Patients with Cardiomyopathy Display Non-Desensitized Agonist-Like Effects"Life Sciences. 64・6/7. 465-469 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mitsuru Hayase: "Immune Mechanism of Myocardial Injury Due to Anti-β1-adrenoceptor Autoantibody:Immunohistological Study of Myocardial Disorders"J Cardiovascular Pharmacology. 34. S29-S32 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shinobu Matsui: "Active Immunization of Combined β1-Adrenoceptor and M2-Muscarinic Receptor peptides Induces Cardiac Hypertropy in Rabbits"Journal of Cardiac Failure. 5(3). 246-254 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsui Shinobu: "Myocardial injury due to G-protein coupled receptor-autoimmunity" Japanese Heat Journal. 39・3. 261-274 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 松井 忍: "抗β1受容体による心筋不全-β遮断薬による保護効果-" 心臓. 30・suppl.2. 34-274 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 松井 忍: "G蛋白に共役する心筋膜受容体に対する自己免疫機序による心筋不全" 金沢医科大学総合医学研究所年報. 9. 108-119 (1998)

    • Related Report
      1998 Annual Research Report

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

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