2000 Fiscal Year Annual Research Report

C型肝炎ウイルス遺伝子導入による心筋症モデルの作製

Research Project

Project/Area Number	11557050
Research Institution	KYOTO UNIVERSITY
Principal Investigator	松森昭京都大学, 医学研究科, 助教授 (70135573)
Keywords	C型肝炎ウイルス / 肥大型心筋症 / 拡張型心筋症 / サイトカイン / HLA / エンテロウイルス / 構造蛋白・非構造蛋白 / 超可変領域
Research Abstract	近年さまざまな心疾患においてC型肝炎ウイルス(HCV)の関与が示唆されている。われわれが本プロジェクトで行ったこれまでの検討では、心筋炎・拡張型心筋症・肥大型心筋症の生検標本からPCRを行うと、従来心筋炎の主要な原因と考えられていたエンテロウイルスよりも高い頻度でHCVが検出された。これらのPCR産物の塩基配列を決定することにより、これらはC型肝炎の標準株と高いホモロジーを示すことが明かとなった。さらに、宿主側の要因としてHLAタイプによる疾患感受性を検討したところ、HIA-DRB1^1201はHCV関連拡張型心筋症と、HLA-DRB1^0901,DQB1^*0303はHCV関連肥大型心筋症と関連することが明らかとなり、宿主の免疫応答性が病型を規定する可能性が示唆された。そこで次にわれわれは、HCV関連心筋症のマウスモデルの作成を試みた。HCVはマウスへの感染が報告されていないため、トランスジェニックモデルを作成した。HCVのcoding regionのうち、構造蛋白と非構造蛋白をそれぞれ別々にpCMVプロモーターによりドライブしてpCMV/980,pCMV/NSの2種類の発現プラスミドを作成し、これらによりトランスジェニックマウスを作成した。構造蛋白の過剰発現マウスは2系統、非構造蛋白の過剰発現マウスは1系統得られている。これらのマウスを現在解析中である。また、HCV感染症例の70%以上が慢性化する要因の一つとして超可変領域の多様な変異による免疫監視機構からの逃避が考えられ、現在超可変領域の心筋特異的塩基配列について検討を重ねている。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Matsumori A, et al.: "Amlodipine inhibits the production of cytokine induced by ouabain. Amlodipine inhibits the production of cytokine induced by ouabain."Cytokine. 12. 294-297 (2000)
[Publications] Matsumori A, et al.: "Hepatitis C virus and cardiomyopathy."Herz. 25. 249-254 (2000)
[Publications] Kakio T, et al.: "Roles and relationship of macrophages and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the ischemic and reperfused rat heart."Lab Invest. 80. 1121-1126 (2000)
[Publications] Matsumori A, et al.: "Hepatitis C virus from the hearts of patients with myocarditis and cardiomyopathy."Lab Invest. 80. 1137-1142 (2000)
[Publications] Naruse TK, et al.: "HLA-DQB1^*0601 is primarily associated with the susceptibility to cardiac sarcoidosis."Tissue Antigens. 56. 52-57 (2000)
[Publications] Nakamura K, et al.: "Hepatitis C virus infection in a patient with dermatomyositis and left ventricular dysfunction."Jpn Circ J. 64. 623-626 (2000)
[Publications] Matsumori A, et al.: "Hypertrophic cardiomyopathy as a manifestation of cardiac sarcoidosis."Jpn Circ J. 64. 679-683 (2000)
[Publications] Matsumori A, et al.: "Circulating hepatocyte growth factor as a marker of thrombus formation in unstable angina pectoris."Jpn Circ J. 64. 805-807 (2000)
[Publications] Matsumori A, et al.: "Pimobendan inhibits the activation of transcription factor NF-κB.A mechanism which explains its inhibition of cytokine production and inducible nitric oxide synthase."Life Sci. 67. 2513-2519 (2000)
[Publications] Matsumori A, et al.: "Nifedipine inhibits of transcription factor NF-κB."Life Sci. 67. 2655-2561 (2000)
[Publications] Tadamura E, et al.: "Significant regional heterogeneity of coronary flow reserve in paediatric hypertrophic cardiomyopathy."Eur J Nucl Med. 27. 1340-1348 (2000)
[Publications] Arimura T, et al.: "Characterization of human nebulette gene : A polymorphism in an actin-binding morif is associated with non-familial dilated cardiomyopathy."Human Genetics. 107. 440-451 (2000)
[Publications] Ohashi N, et al.: "Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury."Arterioscler Thromb Vasc Biol. 20. 2521-2526 (2000)
[Publications] Nishimura H, et al.: "Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice."Science. 291. 391-322 (2001)
[Publications] Matsumori A.: "The role of inflammatory mediators in the failing heart : Immunomodulation of cytokines in experimental models of heart failure."Heart Failure Reviews. 6. 129-136 (2001)
[Publications] Sato Y, et al.: "Persistently increased serum concentrations of cardiac troponin T in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes."Circulation. 103. 369-374 (2001)
[Publications] Matsumori A.: "Insights into the pathophysiology of heart failure based on a new concept."Asian Medical Journal. 44. 36-41 (2001)
[Publications] Matsumori A.: "1.3 Cytokines and heart failure : Pathophysiological roles and therapeutic implications."Heart Failure Frontiers in Cardiology ed.by A.Kitabatake,S.Sasayama,G.S.Francis, Springer. 11 (2000)
[Publications] Matsumori A.: "Hepatitis C virus infection in hypertrophic or dilated cardiomyopathy"The Hypertrophied heart N.Takeda,M.Nagano and N.S.Dhalla (eds).Kluwer Academic. 9 (2000)

2000 Fiscal Year Annual Research Report

C型肝炎ウイルス遺伝子導入による心筋症モデルの作製

Principal Investigator

松森 昭 京都大学, 医学研究科, 助教授 (70135573)

Research Products

[Publications] Matsumori A, et al.: "Amlodipine inhibits the production of cytokine induced by ouabain. Amlodipine inhibits the production of cytokine induced by ouabain."Cytokine. 12. 294-297 (2000)

[Publications] Matsumori A, et al.: "Hepatitis C virus and cardiomyopathy."Herz. 25. 249-254 (2000)

[Publications] Kakio T, et al.: "Roles and relationship of macrophages and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the ischemic and reperfused rat heart."Lab Invest. 80. 1121-1126 (2000)

[Publications] Matsumori A, et al.: "Hepatitis C virus from the hearts of patients with myocarditis and cardiomyopathy."Lab Invest. 80. 1137-1142 (2000)

[Publications] Naruse TK, et al.: "HLA-DQB1^*0601 is primarily associated with the susceptibility to cardiac sarcoidosis."Tissue Antigens. 56. 52-57 (2000)

[Publications] Nakamura K, et al.: "Hepatitis C virus infection in a patient with dermatomyositis and left ventricular dysfunction."Jpn Circ J. 64. 623-626 (2000)

[Publications] Matsumori A, et al.: "Hypertrophic cardiomyopathy as a manifestation of cardiac sarcoidosis."Jpn Circ J. 64. 679-683 (2000)

[Publications] Matsumori A, et al.: "Circulating hepatocyte growth factor as a marker of thrombus formation in unstable angina pectoris."Jpn Circ J. 64. 805-807 (2000)

[Publications] Matsumori A, et al.: "Pimobendan inhibits the activation of transcription factor NF-κB.A mechanism which explains its inhibition of cytokine production and inducible nitric oxide synthase."Life Sci. 67. 2513-2519 (2000)

[Publications] Matsumori A, et al.: "Nifedipine inhibits of transcription factor NF-κB."Life Sci. 67. 2655-2561 (2000)

[Publications] Tadamura E, et al.: "Significant regional heterogeneity of coronary flow reserve in paediatric hypertrophic cardiomyopathy."Eur J Nucl Med. 27. 1340-1348 (2000)

[Publications] Arimura T, et al.: "Characterization of human nebulette gene : A polymorphism in an actin-binding morif is associated with non-familial dilated cardiomyopathy."Human Genetics. 107. 440-451 (2000)

[Publications] Ohashi N, et al.: "Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury."Arterioscler Thromb Vasc Biol. 20. 2521-2526 (2000)

[Publications] Nishimura H, et al.: "Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice."Science. 291. 391-322 (2001)

[Publications] Matsumori A.: "The role of inflammatory mediators in the failing heart : Immunomodulation of cytokines in experimental models of heart failure."Heart Failure Reviews. 6. 129-136 (2001)

[Publications] Sato Y, et al.: "Persistently increased serum concentrations of cardiac troponin T in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes."Circulation. 103. 369-374 (2001)

[Publications] Matsumori A.: "Insights into the pathophysiology of heart failure based on a new concept."Asian Medical Journal. 44. 36-41 (2001)

[Publications] Matsumori A.: "1.3 Cytokines and heart failure : Pathophysiological roles and therapeutic implications."Heart Failure Frontiers in Cardiology ed.by A.Kitabatake,S.Sasayama,G.S.Francis, Springer. 11 (2000)

[Publications] Matsumori A.: "Hepatitis C virus infection in hypertrophic or dilated cardiomyopathy"The Hypertrophied heart N.Takeda,M.Nagano and N.S.Dhalla (eds).Kluwer Academic. 9 (2000)

松森昭京都大学, 医学研究科, 助教授 (70135573)