1997 年度実績報告書

心不全の成因における細胞間情報伝達物質の役割の解明と診断治療への応用

研究課題

研究課題/領域番号	08407018
研究機関	京都大学
研究代表者	篠山重威京都大学, 医学研究科, 教授 (70109007)
研究分担者	木原康樹京都大学, 医学研究科, 助手 (40214853) 村上知行京都大学, 医学研究科, 講師 (00190885) 松森昭京都大学, 医学研究科, 講師 (70135573)
キーワード	心不全 / サイトカイン / 一酸化窒素 / インターロイキン / 腫瘍壊死因子 / NO合成酵素 / 免疫 / ホスホジエステラーゼ阻害薬
研究概要	【目的】われわれの開発したEMCウイルスによる心筋炎から心不全を発症するマウスモデルではIL-1β、TNF-αのメッセンジャーRNA(mRNA)は、早期より発現が増加し、IL-1βは慢性期にも発現の亢進が持続した。また、IL-2,IFN-γも慢性期にも発現がみられた。このような心筋炎の慢性期におけるサイトカイン発現の亢進は、心筋炎から拡張型心筋症病態への進展との関連が示唆された。また、ダール食塩感受性ラットの心不全期やラット心筋梗塞後の心不全モデルにおいてもIL-1βなどのサイトカインの発現が亢進しており、これらのサイトカインと心不全の病態との関連が考えられる。近年、われわれの研究によりホスホジエステラーゼ阻害薬などの強心薬のなかにシトカイン産生を抑制する薬剤があることが明らかとなり、心不全の改善効果との関連が示唆された。一方、IL-1β、TNF-α、IFN-γなどのサイトカインは、心筋のiNOSのほか、心内膜、冠血管のiNOSを誘導し、これらのiNOSにより大量に産生されたNOは心機能障害、心筋細胞障害をきたすと考えられる。NOの過剰発現は心不全をはじめとする各種の病態における心筋収縮性の障害に関与している可能性がある。種々のホスホジエステラーゼ阻害薬にはNO産生抑制効果に差がみられ、強心薬としての作用の差と関係している可能性がある。心不全の根底にある病態生理学的機序には、サイトカインやNOによる心機能の抑制が関与することが示唆され、心不全薬にサイトカインやNO産生抑制作用があることが明らかとなった。また、心不全の病態の理解には、従来の神経・内分泌系因子のほかサイトカインなどの免疫系因子との相互作用を考えることが重要であることが明らかとなった。

研究成果
(31件)

すべてその他

すべて文献書誌 (31件)

[文献書誌] Furukawa Y, et al.: "Angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease and preserves graft status in a murine model." Circulation. 93. 333-339 (1996)
[文献書誌] Sasayama S, et al.: "Role of cytokines in the syndrome of heart failure." Int Med. 35. 60-63 (1996)
[文献書誌] Matsumori A, et al.: "Increased circulating hepatocyte growth factor in the early stage of acute myocardial infarction." Biochem Biophy Res Commun. 221. 391-395 (1996)
[文献書誌] Furukawa Y, et al.: "Immunomodulation by an adenylate cyclase activator,NKH477,in vivo and in vitro." Clin Immunol Immunopathol. 79. 25-35 (1996)
[文献書誌] Hasegawa K, et al.: "Endothelin-1 and its receptor in hypertrophic cardiomyopathy." Hypertension. 27. 254-264 (1996)
[文献書誌] Matsumori A, et al.: "Detection of hepatitis C virus RNA from the heart of patients with hypertrophic cardiomyopathy." Biochem Biophys Res Commun. 222. 678-682 (1996)
[文献書誌] Matsumori A, et al.: "Antimyosin antibody imaging in clinical myocarditis and cardiomyopathy : principle and application." Int Cardiol. 54. 183-190 (1996)
[文献書誌] Matsumori A, et al.: "Inotropic agents differentially inhibit the induction of nitric oxide synthase by endotoxin in cultured macrophages." Life Sci. 59. PL121-PL125 (1996)
[文献書誌] LiL-X, et al.: "Comparative study of 201TI-scintigraphic image and myocardial pathologic findings in patients with dilated cardiomyopathv." Nucl Med. 10. 307-314 (1996)
[文献書誌] Nakamura H, et al.: "A pathogenic mechanisms of chronic ongoing myocarditis." Jpn Circ J. 60. 609-617 (1996)
[文献書誌] Matsumori A, et al.: "Differential modulation of cytokine production by drugs : Implication for therapy in heart failure." J Mol Cell Cardiol. 28. 2491-2499 (1996)
[文献書誌] Sasayama S, et al.: "Vesnarinone : A Potential Cytokine Inhibitor." J Cardiac Failure. 2. 251-258 (1996)
[文献書誌] Shioi T, et al.: "Persistent expression of cytokine in the chronic stage of viral myocarditis in mice." Circulation. 94. 2930-2937 (1996)
[文献書誌] Matsumori A, et al.: "Newer aspects of pathogenesis of heart failure : Hepatitis C virus infection in myocarditis and cardiomyopathy." J Cardiac Failure. 2. S187-S194 (1996)
[文献書誌] Sasayama S, et al.: "Immunomodulation : A new horizon for medical treatmento of heart failure." J Cardiac Failure. 2. S287-S294 (1996)
[文献書誌] Tadamura E, et al.: "Myocardial metabolic changes in hypertrophic cardiomyopathy." J Nucl Med. 37. 572-577 (1996)
[文献書誌] Nakamura H, et al.: "Autoimmune response in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice." Circulation. 94. 3348-3354 (1996)
[文献書誌] Sasayama S, et al.: "Immunomodulatory therapy and survival with cardiac disease." Heart Failure Reviews. 1. 221-227 (1996)
[文献書誌] Sato Y, et al.: "Elevated circulating levels of tumor necrosis factor in patients with mitral valve disease and ventricular septum defect." Heart Vessels. 11. 218-220 (1996)
[文献書誌] Wang W-Z, et al.: "Beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis : A possible mechanism through inhibition of nitric oxide production." Circulation. 95. 245-251 (1997)
[文献書誌] Sato Y, et al.: "Measuring serum aminoterminal type III procollagen peptide,7S domain of type IV collagen,and cardiac troponin T in patients with idiopathic dilated cardiomyopathy and secondary cardiomyopathy." HEART. 78. 505-508 (1997)
[文献書誌] Hirozane T, et al.: "Prolongation of murine cardiac allograft survival with vesnarinone." J Mol Cell Cardiol. 29. 67-76 (1997)
[文献書誌] Matsumori A, et al.: "Plasma levels of the monocyte chemotactic and activating factor/monocyte chemotactic protein-1 are elevated in patients with acute myocardial infarction." J Mol Cell Cardiol. 29. 419-423 (1997)
[文献書誌] Shioi T, et al.: "Protective role of Interleukin-12 in viral myocarditis." J Mol Cell Cardiol. 29. 2327-2334 (1997)
[文献書誌] One K, et al.: "Enhanced expression of hepatocyte growth factor/c-met by myocardial ischemia and reperfusion in a rat model." Circulation. 95. 2552-2558 (1997)
[文献書誌] Yamada T, et al.: "Indium-111 antimyosin antibody imaging and thallium-201 imaging : A comparative myocardial scintigraphic study using SPECT in patients with myocarditis and dilated cardiomyopathy." Jpn Circ J. 61. 827-835 (1997)
[文献書誌] Matsumori A, et al.: "Modulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain." Circulation. 96. 1501-1506 (1997)
[文献書誌] Matsumori A, et al.: "Amiodarone inhibits production of tumor necrosis factor-α by human mononuclear cells. A possible mechanism for its effect in heart failure." Circulation. 96. 1386-1389 (1997)
[文献書誌] Shioi T, et al.: "Increased expression of interleukin-1β and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP-1) in the hypertrophied and failing heart with pressure overload." Circ Res. 81. 664-671 (1997)
[文献書誌] Matsumori A, et al.: "Edited by Sasayama S,Springer-Verlag,Tokyo" Cytokines and heart failure : Immunomodulating agents for the management of heart failure.In New Horizons for Failing Heart Syndrome., 14 (1996)
[文献書誌] Sasayama S, et al.: "Edited by Endoh M,Morad M,Scholz H,Iijima T,Springer-Verlag,Tokyo" Immunomodulating effects as new aspects of a positive inotropic agent. In Molecular and Cellular Mechanism of Cardiovascular Regulation., 11 (1996)

1997 年度 実績報告書

心不全の成因における細胞間情報伝達物質の役割の解明と診断治療への応用

研究代表者

篠山 重威 京都大学, 医学研究科, 教授 (70109007)

研究成果

[文献書誌] Furukawa Y, et al.: "Angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease and preserves graft status in a murine model." Circulation. 93. 333-339 (1996)

[文献書誌] Sasayama S, et al.: "Role of cytokines in the syndrome of heart failure." Int Med. 35. 60-63 (1996)

[文献書誌] Matsumori A, et al.: "Increased circulating hepatocyte growth factor in the early stage of acute myocardial infarction." Biochem Biophy Res Commun. 221. 391-395 (1996)

[文献書誌] Furukawa Y, et al.: "Immunomodulation by an adenylate cyclase activator,NKH477,in vivo and in vitro." Clin Immunol Immunopathol. 79. 25-35 (1996)

[文献書誌] Hasegawa K, et al.: "Endothelin-1 and its receptor in hypertrophic cardiomyopathy." Hypertension. 27. 254-264 (1996)

[文献書誌] Matsumori A, et al.: "Detection of hepatitis C virus RNA from the heart of patients with hypertrophic cardiomyopathy." Biochem Biophys Res Commun. 222. 678-682 (1996)

[文献書誌] Matsumori A, et al.: "Antimyosin antibody imaging in clinical myocarditis and cardiomyopathy : principle and application." Int Cardiol. 54. 183-190 (1996)

[文献書誌] Matsumori A, et al.: "Inotropic agents differentially inhibit the induction of nitric oxide synthase by endotoxin in cultured macrophages." Life Sci. 59. PL121-PL125 (1996)

[文献書誌] LiL-X, et al.: "Comparative study of 201TI-scintigraphic image and myocardial pathologic findings in patients with dilated cardiomyopathv." Nucl Med. 10. 307-314 (1996)

[文献書誌] Nakamura H, et al.: "A pathogenic mechanisms of chronic ongoing myocarditis." Jpn Circ J. 60. 609-617 (1996)

[文献書誌] Matsumori A, et al.: "Differential modulation of cytokine production by drugs : Implication for therapy in heart failure." J Mol Cell Cardiol. 28. 2491-2499 (1996)

[文献書誌] Sasayama S, et al.: "Vesnarinone : A Potential Cytokine Inhibitor." J Cardiac Failure. 2. 251-258 (1996)

[文献書誌] Shioi T, et al.: "Persistent expression of cytokine in the chronic stage of viral myocarditis in mice." Circulation. 94. 2930-2937 (1996)

[文献書誌] Matsumori A, et al.: "Newer aspects of pathogenesis of heart failure : Hepatitis C virus infection in myocarditis and cardiomyopathy." J Cardiac Failure. 2. S187-S194 (1996)

[文献書誌] Sasayama S, et al.: "Immunomodulation : A new horizon for medical treatmento of heart failure." J Cardiac Failure. 2. S287-S294 (1996)

[文献書誌] Tadamura E, et al.: "Myocardial metabolic changes in hypertrophic cardiomyopathy." J Nucl Med. 37. 572-577 (1996)

[文献書誌] Nakamura H, et al.: "Autoimmune response in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice." Circulation. 94. 3348-3354 (1996)

[文献書誌] Sasayama S, et al.: "Immunomodulatory therapy and survival with cardiac disease." Heart Failure Reviews. 1. 221-227 (1996)

[文献書誌] Sato Y, et al.: "Elevated circulating levels of tumor necrosis factor in patients with mitral valve disease and ventricular septum defect." Heart Vessels. 11. 218-220 (1996)

[文献書誌] Wang W-Z, et al.: "Beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis : A possible mechanism through inhibition of nitric oxide production." Circulation. 95. 245-251 (1997)

[文献書誌] Sato Y, et al.: "Measuring serum aminoterminal type III procollagen peptide,7S domain of type IV collagen,and cardiac troponin T in patients with idiopathic dilated cardiomyopathy and secondary cardiomyopathy." HEART. 78. 505-508 (1997)

[文献書誌] Hirozane T, et al.: "Prolongation of murine cardiac allograft survival with vesnarinone." J Mol Cell Cardiol. 29. 67-76 (1997)

[文献書誌] Matsumori A, et al.: "Plasma levels of the monocyte chemotactic and activating factor/monocyte chemotactic protein-1 are elevated in patients with acute myocardial infarction." J Mol Cell Cardiol. 29. 419-423 (1997)

[文献書誌] Shioi T, et al.: "Protective role of Interleukin-12 in viral myocarditis." J Mol Cell Cardiol. 29. 2327-2334 (1997)

[文献書誌] One K, et al.: "Enhanced expression of hepatocyte growth factor/c-met by myocardial ischemia and reperfusion in a rat model." Circulation. 95. 2552-2558 (1997)

[文献書誌] Yamada T, et al.: "Indium-111 antimyosin antibody imaging and thallium-201 imaging : A comparative myocardial scintigraphic study using SPECT in patients with myocarditis and dilated cardiomyopathy." Jpn Circ J. 61. 827-835 (1997)

[文献書誌] Matsumori A, et al.: "Modulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain." Circulation. 96. 1501-1506 (1997)

[文献書誌] Matsumori A, et al.: "Amiodarone inhibits production of tumor necrosis factor-α by human mononuclear cells. A possible mechanism for its effect in heart failure." Circulation. 96. 1386-1389 (1997)

[文献書誌] Shioi T, et al.: "Increased expression of interleukin-1β and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP-1) in the hypertrophied and failing heart with pressure overload." Circ Res. 81. 664-671 (1997)

[文献書誌] Matsumori A, et al.: "Edited by Sasayama S,Springer-Verlag,Tokyo" Cytokines and heart failure : Immunomodulating agents for the management of heart failure.In New Horizons for Failing Heart Syndrome., 14 (1996)

[文献書誌] Sasayama S, et al.: "Edited by Endoh M,Morad M,Scholz H,Iijima T,Springer-Verlag,Tokyo" Immunomodulating effects as new aspects of a positive inotropic agent. In Molecular and Cellular Mechanism of Cardiovascular Regulation., 11 (1996)

1997 年度実績報告書

篠山重威京都大学, 医学研究科, 教授 (70109007)