1999 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 Category	Grant-in-Aid for Scientific Research (B)
Research Institution	Kyoto University
Principal Investigator	松森昭京都大学, 大学院・医学研究科, 助教授 (70135573)
Keywords	C型肝炎ウイルス / ウイルス / 心筋症 / 心筋炎 / HLA / 遺伝子 / トランスジェニック / マウス
Research Abstract	【目的】近年、我々が肥大型心筋症をはじめとしていくつかの心疾患にC型肝炎ウイルス(HCV)感染が関与していることを発見して以来、国内外において同様の報告が相次ぎ、心筋症・心筋炎の新たな病因として注目されている。これまでに我々が検討した心疾患患者においては、心筋炎12例中4例(33.3%)、拡張型心筋症26例中3例(11.5%)、肥大型心筋症23例中6例(26%)の生検標本切片でHCVゲノムを検出し得た。これは従来主な病原ウイルスと考えられていたエンテロウイルスよりも高い数値である。さらにnested PCR法によるマイナス鎖の同定をすすめている。 HCV感染が70%以上の症例で慢性化する要因の一つとして、超可変領域(HVR;hypervariable region)の多様な変異による免疫監視機構からの逃避が挙げられる。心筋特異的塩基配列について現在検討を重ねている。このウイルス側の要因に加えて、宿主側の要因として、HCV肝硬変の疾患感受性にHLAジェノタイプによる宿主側の感受性の差異が注目されている。HLA-A11,B67は拡張型心筋症と、またHLA-DB1^0407,DRB1^0901,DQB1^0303は肥大型心筋症と関連することが明かとなっている。とくにDRB1^0901,DQB1^*0303はC型肝炎発症者ではむしろ減少していることが報告されており、HLAタイプにより拡張型心筋症・肥大型心筋症・肝炎・無症候性キャリアなどの発症の違いが説明される可能性が高い。また、HCVの各タンパクをコードする遺伝子の発現ベクターがすでに完成している。現在、これらを用いて遺伝子導入マウスを作製中である。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Jurukawa Y.et al.: "Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries"Circ Res. 84. 306-314 (1999)
[Publications] Ono K.et al.: "Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1"Lab Invest. 79. 195-203 (1999)
[Publications] Okada M.et al.: "Hepatocyte growth factor is a major mediator in heparin-induced angiogenesis"Biochem Biophys Res Commun. 255. 80-87 (1999)
[Publications] Iwasaki A.et al.: "Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis"J Am Coll Cardiol. 33. 1400-1407 (1999)
[Publications] Matsumori A.et al.: "Apical hypertrophic cardiomyopathy and hepatitis C virus infection"Jpn Circ J. 63. 433-438 (1999)
[Publications] Hwang MW.et al.: "FTY720, a new immunosuppressant, promotes long-term graft survival and inhibits the progression of graft coronary artery disease in a murine model of cardiac transplantation"Circulation. 100. 1322-1329 (1999)
[Publications] Hara M.et al.: "Mast cells apoptosis of cardiomyocytes and proliferation of other intramyocardial cells in vivo"Circulation. 100. 1443-1449 (1999)
[Publications] Nishio R.et al.: "Treatment of experimental viral myocarditis with interleukin-10"Circulation. 100. 1102-1108 (1999)
[Publications] Ono K.et al.: "Contribution of endothelin-1 to myocardial injury in a murine model of myocarditis.Acute effects of bosentan, an endothelin receptor antagonist"Circulation. 100. 1823-1829 (1999)
[Publications] Furukawa Y.et al.: "Cytokine gene expression during the development of graft coronary artery disease in mice"Jpn Circ J. 63. 775-782 (1999)
[Publications] Matsumori A.et al.: "High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: A possible mechanism of digitalis toxicity"Jpn Circ J. 63. 934-940 (1999)
[Publications] Gwathmey JK.et al.: "Cellular and molecular remodeling in an animal model of dilated cardiomyopathy treated with the b-blocker carteolol"Am J Physiol. 276. H1678-H1690 (1999)
[Publications] Ono K, Matsumori A.: "Inflammatory heart disease."In Congestive heart failure, Second Edition, edited by Jeffrey D. Hosenpud and Barry H. Grenberg. Lippincott Williams & Wilkins, Philadelphia.. 11 (1999)

1999 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, 大学院・医学研究科, 助教授 (70135573)

Research Products

[Publications] Jurukawa Y.et al.: "Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries"Circ Res. 84. 306-314 (1999)

[Publications] Ono K.et al.: "Prevention of myocardial reperfusion injury in rats by an antibody against monocyte chemotactic and activating factor/monocyte chemoattractant protein-1"Lab Invest. 79. 195-203 (1999)

[Publications] Okada M.et al.: "Hepatocyte growth factor is a major mediator in heparin-induced angiogenesis"Biochem Biophys Res Commun. 255. 80-87 (1999)

[Publications] Iwasaki A.et al.: "Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis"J Am Coll Cardiol. 33. 1400-1407 (1999)

[Publications] Matsumori A.et al.: "Apical hypertrophic cardiomyopathy and hepatitis C virus infection"Jpn Circ J. 63. 433-438 (1999)

[Publications] Hwang MW.et al.: "FTY720, a new immunosuppressant, promotes long-term graft survival and inhibits the progression of graft coronary artery disease in a murine model of cardiac transplantation"Circulation. 100. 1322-1329 (1999)

[Publications] Hara M.et al.: "Mast cells apoptosis of cardiomyocytes and proliferation of other intramyocardial cells in vivo"Circulation. 100. 1443-1449 (1999)

[Publications] Nishio R.et al.: "Treatment of experimental viral myocarditis with interleukin-10"Circulation. 100. 1102-1108 (1999)

[Publications] Ono K.et al.: "Contribution of endothelin-1 to myocardial injury in a murine model of myocarditis.Acute effects of bosentan, an endothelin receptor antagonist"Circulation. 100. 1823-1829 (1999)

[Publications] Furukawa Y.et al.: "Cytokine gene expression during the development of graft coronary artery disease in mice"Jpn Circ J. 63. 775-782 (1999)

[Publications] Matsumori A.et al.: "High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: A possible mechanism of digitalis toxicity"Jpn Circ J. 63. 934-940 (1999)

[Publications] Gwathmey JK.et al.: "Cellular and molecular remodeling in an animal model of dilated cardiomyopathy treated with the b-blocker carteolol"Am J Physiol. 276. H1678-H1690 (1999)

[Publications] Ono K, Matsumori A.: "Inflammatory heart disease."In Congestive heart failure, Second Edition, edited by Jeffrey D. Hosenpud and Barry H. Grenberg. Lippincott Williams & Wilkins, Philadelphia.. 11 (1999)

松森昭京都大学, 大学院・医学研究科, 助教授 (70135573)