| Project/Area Number |
13670753
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | KANAZAWA MEDICAL UNIVERSITY |
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Principal Investigator |
MATSUI Shinobu KANAZAWA MEDICAL UNIVERSITY, Medical Research Institute, Professor, 総合医学研究所, 教授 (00064600)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASE Mituru KANAZAWA MEDICAL UNIVERSITY, Department of Clinical Pathology, Lecturer, 医学部, 講師 (90064592)
YAMAGUCHI Nobuo KANAZAWA MEDICAL UNIVERSITY, Department of Serology, Professor, 医学部, 教授 (10106916)
KATSUDA Shogo KANAZAWA MEDICAL UNIVERSITY, Department of Pathology, Professor, 医学部, 教授 (40110613)
KURIHARA Takayuki KANAZAWA MEDICAL UNIVERSITY, Medical Research Institute, Lecturer, 総合医学研究所, 講師 (20064595)
ASAJI Takayosi KANAZAWA MEDICAL UNIVERSITY, Department of Cardiology, Lecturer, 医学部, 講師 (00183137)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | dilated cardiomyopathy / β1-adrenoceptor / muscarinic-2 receptor / autoantibody / immunoabsorption / autoimmune disease / SCIDマウス / β_1受容体 |
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| 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 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 year 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. These clinical and experimental findings suggest that these anti-β1-adrenoceptor and M2-muscarinic receptor autoantibodies are of pathogenic importance in the development of dilated cardiomyopathy in vivo.
Based on these findings, we attempted to develope the immunoadborption colume which is able to extract anti-β1-adrenoceptor autoantibodies, selectively. The efficacy of this colume was about 70% against the sera of anti-β1-adrenoceptor autoantibody-positive absorbing-patients with dilated cardiomyopathy. Thereafter, rabbits immunized with β1-peptide or M2-peptide underwent immunoabsorption with anti-IgG colume. As a result, anti-IgG immunoabsorption therapy was performed safely and resulted in significant reduction of titer of anti-β1-adrenoceptor and M2-muscarmnic receptor autoantibodies. Now, we are trying to assess the effectiveness and safty using the rabbits with experimental autoimmue cardiomyopaty induced by immunization of β1-peptide.
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