1998 Fiscal Year Annual Research Report

C型肝炎ウイルスに遺伝子導入による心筋症モデルの作製

Research Project

Project/Area Number	10470164
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 / 心筋症 / 拡張型心筋症 / 肥大型心筋症 / 心筋炎 / PCR法 / 肝炎 / ウイルス
Research Abstract	【目的】近年、われわれの研究により、心筋症の病因としてC型肝炎ウイルス(HCV)感染の重要性が明らかになった。拡張型心筋症53例中8例(15.1%)、肥大型心筋症66例中11例(16.7%)において血清HCV抗体が陽性であった。これは虚血性心疾患40例中1例(2.5%)に比し有意に高頻度であった(p<0.05)。SSCP(single strand conformation polymorphism)法による心筋症患者でのゲノム解析では、超可変領域(HVR)め塩基多様度が高度で、多数のクローンが同一症例にみられることがあり、これらの変異により心筋に親和性の高いウイルスゲノムが出現する可能性が考えられた。また、多施設の共同研究としてわが国における心筋症におけるHCV感染およびHCV抗体陽性者の臨床像に関するアンケート調査を行った結果、拡張型心筋症619例中37例(6.0%)、肥大型心筋症585例中61例(10.4%)において血清HCV抗体が陽性であった。一方、HCV抗体陽性者は11,210例中604例(5.4%)に見られた。このHCV抗体陽性例の臨床診断名は不整脈、高血圧症をはじめとして多くの疾患でみられ、HCV感染は心筋症以外の心疾患にも関与している可能性が示唆された。研究代表者はホルマリン固定パラフィン切片がらのHCVゲノム検出法を確定し、剖検心を用いた検討が可能となった。剖検心では心筋炎4/12(33.3%)、拡張型心筋症3/26(11.5%)、肥大型心筋症6/23(26.0%)と高頻度にHCVゲノムに検出した。WHO/世界心臓連盟の心筋症科学委員会による心筋症のウイルス病因に関する国際共同研究において、研究代表者はHCV解析を担当したが、拡張型心筋症および心筋炎の生検標本22例中6例(27.3%)からHCVゲノムを検出し、検討したウイルス中で最も高頻度であった。

Research Products
(18 results)

All Other

All Publications (18 results)

[Publications] Wang W-Z, et al.: "Protective effects of Mu-Fang-Ji-Tang against myocardial injury in a murine model of congestive heart failure induced by viral myocarditis." Life Sci. 62. 1139-1147 (1998)
[Publications] Okada M, et al.: "Cyclical stretch upregulates the prodection of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells." Arterioscler Thromb Vasc Biol. 18. 894-901 (1998)
[Publications] Ono K, et al.: "Cytokine gene expression after myocardial infarction in rat hearts. Possible implication in left ventricular remodeling." Circulation. 98. 149-156 (1998)
[Publications] Matsumori A.: "Calcium channel blocker-induced protection against cardiovascular damage." Int.J.Cardiol.suppl.62. S39-S46 (1998)
[Publications] Matsumori A.: "The use of cytokine inhibitors A new therapeutic insight into heart failure." Int.J.Cardiol.suppl.62. S3-S12 (1998)
[Publications] Matsumori A, et al.: "Circulating hepatocyte growth factor as an early marker of arterial thrombus formation." Jpn Circ J. 62. 311-313 (1998)
[Publications] Matsumori A, et al.: "Hepatitis C virus infection and heart diseases. A multicenter study in Japan." Jpn Circ J. 62. 389-391 (1998)
[Publications] Sato Y, et al.: "Serum concentration of cardiac troponin T in patients with cardiomyopathy-A possible mechanism of acute heart failure-" HEART. 80. 209-210 (1998)
[Publications] Yamada T, et al.: "Myosin light chain I trade:A simple marker for the severity and prognosis of patients with acute myocardial infarction." Am Heart J. 135. 329-334 (1998)
[Publications] Nishio R, et al.: "Denopamine, a β1-adrenergic agonist, prolongs survival in a murine model of congestive heart failure induced by viral myocarditis. Suppression of tumor necrosis factor-a production in the heart." J Am Coll Cardiol. 32. 808-815 (1998)
[Publications] Matsumori A, et al.: "Immediate increase in circulating hepatocyte growth factor/scatter factor by heparin." J Mol Cell Cardiol. 30. 2145-2149 (1998)
[Publications] Matsumori A, et al.: "Hepatitis C virus infection and hypertrophic cardiomyopathy." Ann Int Med. 129. 749-750 (1998)
[Publications] Furukawa 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. 225. 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. (in press).
[Publications] Matsumori A, et al.: "Apical hypertrophic cardiomyopathy and hepatitis C virus infection." Jpn Circ J. (in press).
[Publications] Matsumori A,et al.: "Coronary reperfusion and cytokines." Edited by Abiko Y, Karmazyn M Springer-Verlag, Tokyo, 157-177(20) (1998)

1998 Fiscal Year Annual Research Report

C型肝炎ウイルスに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] Wang W-Z, et al.: "Protective effects of Mu-Fang-Ji-Tang against myocardial injury in a murine model of congestive heart failure induced by viral myocarditis." Life Sci. 62. 1139-1147 (1998)

[Publications] Okada M, et al.: "Cyclical stretch upregulates the prodection of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells." Arterioscler Thromb Vasc Biol. 18. 894-901 (1998)

[Publications] Ono K, et al.: "Cytokine gene expression after myocardial infarction in rat hearts. Possible implication in left ventricular remodeling." Circulation. 98. 149-156 (1998)

[Publications] Matsumori A.: "Calcium channel blocker-induced protection against cardiovascular damage." Int.J.Cardiol.suppl.62. S39-S46 (1998)

[Publications] Matsumori A.: "The use of cytokine inhibitors A new therapeutic insight into heart failure." Int.J.Cardiol.suppl.62. S3-S12 (1998)

[Publications] Matsumori A, et al.: "Circulating hepatocyte growth factor as an early marker of arterial thrombus formation." Jpn Circ J. 62. 311-313 (1998)

[Publications] Matsumori A, et al.: "Hepatitis C virus infection and heart diseases. A multicenter study in Japan." Jpn Circ J. 62. 389-391 (1998)

[Publications] Sato Y, et al.: "Serum concentration of cardiac troponin T in patients with cardiomyopathy-A possible mechanism of acute heart failure-" HEART. 80. 209-210 (1998)

[Publications] Yamada T, et al.: "Myosin light chain I trade:A simple marker for the severity and prognosis of patients with acute myocardial infarction." Am Heart J. 135. 329-334 (1998)

[Publications] Nishio R, et al.: "Denopamine, a β1-adrenergic agonist, prolongs survival in a murine model of congestive heart failure induced by viral myocarditis. Suppression of tumor necrosis factor-a production in the heart." J Am Coll Cardiol. 32. 808-815 (1998)

[Publications] Matsumori A, et al.: "Immediate increase in circulating hepatocyte growth factor/scatter factor by heparin." J Mol Cell Cardiol. 30. 2145-2149 (1998)

[Publications] Matsumori A, et al.: "Hepatitis C virus infection and hypertrophic cardiomyopathy." Ann Int Med. 129. 749-750 (1998)

[Publications] Furukawa 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. 225. 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. (in press).

[Publications] Matsumori A, et al.: "Apical hypertrophic cardiomyopathy and hepatitis C virus infection." Jpn Circ J. (in press).

[Publications] Matsumori A,et al.: "Coronary reperfusion and cytokines." Edited by Abiko Y, Karmazyn M Springer-Verlag, Tokyo, 157-177(20) (1998)

松森昭京都大学, 医学研究科, 助教授 (70135573)