| Project/Area Number |
10670679
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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 Medical Research Institute, KANAZAWA MEDICAL UNIVERSITY Professor, 総合医学研究所, 教授 (00064600)
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| 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)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| 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)
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| Keywords | Dilated 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 |
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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 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.
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