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Role of Inflammatory Cytokines in the Development and Progression of Ischemic Heart Diseases-Experimental and Clinical Studies-

Research Project

Project/Area Number 05454274
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionKyushu University

Principal Investigator

SHIMOKAWA Hiroaki  Kyushu University Assoc.Prof., 医学部, 助教授 (00235681)

Co-Investigator(Kenkyū-buntansha) UENO Hikaru  Kyushu University Assis.Prof., 医学部, 講師 (50260378)
SUEISHI Katsuo  Kyushu University Professor, 医学部, 教授 (70108710)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1994: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1993: ¥3,700,000 (Direct Cost: ¥3,700,000)
Keywordsinflammatory cytokines / ischemic heart disease / arteriosclerosis / coronary artery spasm / coronary thrombosis / myocardial infarction / サイトカイン / 細胞増殖因子 / 冠動脈硬化 / 冠等縮 / 冠□縮
Research Abstract

(A)Basic Research
(1) Chrocic Treatment with interleukin (IL) -1beta causes arteriosclerotic changes and vasospastic responses to autacoids in porcine coronary arteries in vivo.
(2) Chronic treatment with IL-1alpha or tumor necrosis factor-alpha (TNF-alpha) also caused similar changes of the coronary artery, showing the redundant effects of inflammatory cytokines.
(3) The histological and functiona changes of the coronary artery induced by IL-1beta were mediated by both platelet-derived growth factor and fibroblast growth factor-2.
(4) A selective tyrosine kinase inhibitor, ST638, markedly suppressed the histological and functional changes of the coronary artery induced by IL-1beta.
(5) In the pathogenesis of coronary artery spasm at the inflammatory coronary lesions, a PKC-mediated pathway plays an important role, while the contribution of Ca^<2+>release from the intracellular store site may be minimal.
(B)Clinical Research
(6) Three types of changes in the plasma levels of cytokines were noted in patients with acute myocardial infarction ; transient increase (plasma levels of IL-6, generation capacity for IL-1alpha), sustained increase (plasma levels of macrophagecolony stimulating factor and generation capacity for IL-1beta), and late increase (plasma levels of interferon-gamma).
(7) In patients with ischemic heart disease, plasma levels of macrophage colony stimulating factor were increased, while those of transforming growth factor-beta were decreased.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Shimokawa H.et al: "Chronic treatment with Interleukin-1β induces coronary intimal lesions and vasospastic responses in pigs in vivo." J Clin Invest.97. 769-776 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokawa H.et al.: "Endothelial Gi protein expression is markedly low in human coronary microvessels." J Cardiovasc Pharmacol.27. 297-302 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kadokami T.et al.: "Coronary artery spasm does not depend on the intracellular calcium store but is substantially mediated by the protein kinase C-mediated pathway in a swine model with interleukin-1β." Circulation. in press.(1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokawa H,Takeshita A.: "Endothelium-dependent regulation of the cardiovascular system." Internal Medicine. 34. 939-946 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokawa H.et al.: "Significance of defective endothelial signal transduction in impaired endothelium-dependent relaxation in atherosclerosis." Gerontology.41. 28-33 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ito A et al.: "Tyrosine Kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced bychronic treatment with interleukin-1β in pigs in vivo." J Clin Invest. 96. 1288-1294 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokawa H,Ito A,Fukumoto Y.et al.: "Chronic treatment with Interleukin-1beta induces coronary intimal lesions and vasospastic responses in pigs in vivo." J Clin Invest.97. 769-776 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokawa H,Tsutsui M,Mizuki T,et al.: "Endothelial Gi protein expression is markedly low in human coronary microvessels" J Cardiovasc Pharmacol.27. 297-302 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kadokami T,Shimokawa H,FukumotoY,et al.: "Coronary artery spasm does not depend on the intracellular calcium store but is substantially mediated by the protein kinase Cmediated pathway in a swine model with interleukin-1beta." Circulation. (in press.). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokawa H,Takeshita A.: "Endothelium dependent regulation of the cardiovascular system." Intern Med. 34. 939-946 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimokawa H,Nakaike R,Takeshita A: "Significance of defective endothelial signal transduction in impaired endothelium dependent relaxation in atherosclerosis." Gerontology. 41. 28-33 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ito A,Shimokawa H,Kadokami T,et al.: "Tyrosine kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced by chronic treatment with interleukin-1beta in pigs in vivo." J Clin Invest. 96. 1228-1294 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ito A.,et al.: "Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm" Circulation. 90. 2425-2431 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tsutsui M.,et al.: "Endothelial Gi protein in human coronary arteries" Eur Heart J. 15. 1261-1266 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakaike R.,et al.: "Effects of L-arginine analogues on vasomotion of isolated coronary arteries" Am J Physiol. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tashiro H.,et al.: "Monocyte-related cytokines in acute myocardial infarction" Am Heart J. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shimokawa H.,et al.: "Significance of defective signal transduction in impaired endothelium-dependent relaxation in atherosclerosis" Gerontology. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shimokawa H.and Vanhoutte P.M.: "The Handbook of Hypertension" Elsevier Science Publishing Co.(in press), (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 下川 宏明: "Annual Review 循環器" 中外出版(in press), (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tagawa H.: "Hyperreactivity of aortic smooth muscle to serotonin is related to the presence of atheroma of Watanabe heritable hyperlipidaemic rabbits." Cardiovascular Research. 27. 2164-2169 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tsutsui M.: "Intracellular magnesium deficiency in acute myocardial infarction." Japanese Heart Jouinal. 34. 391-401 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tashiro H.: "clinical characteristics of patients with spontaneous remission of variant angina." Japanese Circulation Jouinal. 57. 117-122 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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