1997 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	08407018
Research Institution	Kyoto University
Principal Investigator	篠山重威京都大学, 医学研究科, 教授 (70109007)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	【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。

Research Products

(31 results)

All Other

All Publications (31 results)

[Publications] 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)
[Publications] Sasayama S, et al.: "Role of cytokines in the syndrome of heart failure." Int Med. 35. 60-63 (1996)
[Publications] 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)
[Publications] Furukawa Y, et al.: "Immunomodulation by an adenylate cyclase activator,NKH477,in vivo and in vitro." Clin Immunol Immunopathol. 79. 25-35 (1996)
[Publications] Hasegawa K, et al.: "Endothelin-1 and its receptor in hypertrophic cardiomyopathy." Hypertension. 27. 254-264 (1996)
[Publications] 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)
[Publications] Matsumori A, et al.: "Antimyosin antibody imaging in clinical myocarditis and cardiomyopathy : principle and application." Int Cardiol. 54. 183-190 (1996)
[Publications] 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)
[Publications] 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)
[Publications] Nakamura H, et al.: "A pathogenic mechanisms of chronic ongoing myocarditis." Jpn Circ J. 60. 609-617 (1996)
[Publications] 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)
[Publications] Sasayama S, et al.: "Vesnarinone : A Potential Cytokine Inhibitor." J Cardiac Failure. 2. 251-258 (1996)
[Publications] Shioi T, et al.: "Persistent expression of cytokine in the chronic stage of viral myocarditis in mice." Circulation. 94. 2930-2937 (1996)
[Publications] 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)
[Publications] Sasayama S, et al.: "Immunomodulation : A new horizon for medical treatmento of heart failure." J Cardiac Failure. 2. S287-S294 (1996)
[Publications] Tadamura E, et al.: "Myocardial metabolic changes in hypertrophic cardiomyopathy." J Nucl Med. 37. 572-577 (1996)
[Publications] Nakamura H, et al.: "Autoimmune response in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice." Circulation. 94. 3348-3354 (1996)
[Publications] Sasayama S, et al.: "Immunomodulatory therapy and survival with cardiac disease." Heart Failure Reviews. 1. 221-227 (1996)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Hirozane T, et al.: "Prolongation of murine cardiac allograft survival with vesnarinone." J Mol Cell Cardiol. 29. 67-76 (1997)
[Publications] 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)
[Publications] Shioi T, et al.: "Protective role of Interleukin-12 in viral myocarditis." J Mol Cell Cardiol. 29. 2327-2334 (1997)
[Publications] 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)
[Publications] 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)
[Publications] Matsumori A, et al.: "Modulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain." Circulation. 96. 1501-1506 (1997)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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 Fiscal Year Annual Research Report

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

Principal Investigator

篠山 重威 京都大学, 医学研究科, 教授 (70109007)

Research Products

[Publications] 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)

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

[Publications] 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)

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

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

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

[Publications] 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)

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

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

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

篠山重威京都大学, 医学研究科, 教授 (70109007)