• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Experimental and Clinical Studies on the Role of Inflammatory Mechanisms in the Pathogenesis of Ischemic Heart Disease

Research Project

Project/Area Number 09470169
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SHIMOKAWA Horoaki  Kyushu Univ. Graduate Sch., Dept. of Cardiovasc Med., Asso. Pro., 大学院・医学系研究科, 助教授 (00235681)

Co-Investigator(Kenkyū-buntansha) MOHRI Masahiro  Kyushu Univ. Sch. of Med., Dept. of Cardiovasc Med., Assist. Pro., 医学部, 助手 (60264032)
MARUYAMA Ikuro  Kagoshima Univ. Dept. of Laboratory Med., Prof., 医学部, 教授 (20082282)
SUEISHI Katuso  Kyushu Univ. Graduate Sch., Dept. of Pathology, Asso. Pro., 大学院・医学系研究科, 教授 (70108710)
SATOH Shinji  Kyushu Univ. Graduate Sch., Dept. of Cardiovasc Med., Adjunct Assist. Prof., 大学院・医学系研究科, 助手 (60274445)
OHARA Yuichi  Kyushu Univ. Sch. of Med., Dept. of Cardiovasc Med., Adjunct Assist. Prof., 医学部, 助手 (90185364)
ICHKI Toshihiro  Kyushu Univ. Sch. of Med., Dept. of Cardiovasc Med., Asso. Adjunct Assist. Prof. (80311843)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 1999: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1998: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1997: ¥5,100,000 (Direct Cost: ¥5,100,000)
Keywordscytokines / atherosclerosis. / coronary artery spasm / vascular remodeling / nitric oxide / small G proteins / Rho-kinase / gene therapy / Rho-kinase / 炎症性サイトカイン / 虚血性心疾患 / マクロファージ / 血管外膜 / 炎症 / 冠攣縮
Research Abstract

(Experimental studies)
1. The long-term adventitial treatment with IL-1βresulted in the development of vascular remodeling and neointimal formation of the porcine coronary artery in vivo, whereas endothelial vasodilator functions were fairly preserved.
2. In this porcine model, inducible NO synthase (iNOS) was transiently expressed in VSMC and exerted an inhibitory effect against vascular lesion formation in vivo.
3. Regarding the molecular mechanism of the coronary artery spasm in this porcine model, it was shown that Rho-kinase is upregulated and inhibits myosin phosphatase, resulting in the increased myosin phosphorylations and hypercontractions of VSMC.
4. We have established the method of in vivo gene transfer into the coronary artery in vivo using the infiltrator balloon angioplasty catheter (IABC). Using this novel method, we were able to inhibit the neointimal formation after balloon injury in porcine coronary arteries by overexpressing CNP in vivo.
5. The long-term inhibitation of Rho-kinase by either hydroxyfasudil (a specific inhibitor of Rho-kinase) or in vivo gene transfer of dominant negative Rho-kinase resulted in the regression of vascular remodeling caused by inflammatory cytokines.
(Clinical studies)
In patients with coronary artery disease, the plasma levels of macrophage-colony stimulating factor (M-CSF) were increased while those of transforming factor-b (TGF-b) were decreased, thus stimulating the process of atherosclerosis.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Fukumoto Y, Shimokawa H, et al.: "Vasculoprotective role of inducible nitric oxide synthase at inflammatory coronary lesions induced by chronic treatment with interleukin-1b in pigs in vivo."Circulation. 96. 3104-3111 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tashiro H, Shimokawa H, et al.: "Altered plasma levels of cytokines in patients with ischemic heart disease."Coronary Artery Disease. 8. 143-147 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Katsumata N, Shimokawa H, el at.: "Enhanced myosin light chan phosphoryla-tions as a central mechanism for coronary artery spasm in a swine model with interleukin-1b"Circulation. 96. 4357-4363 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyata K, Shimokawa H, ET AL.: "Endothlial vasodilator function is preserved at the spastic/inflammatory coronary lessions in pigs."Circulation. 100. 1432-1437 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimokawa H, Seto M, et al.: "Rho-Kinase-mediated pathway induces enhanced myosin light chain phosphorylations in a swine model of coronary artert spasm."Cardiovascular Research. 43. 1029-1039 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimokawa H.: "Celluar and molecular mechanism of coronary artery spasm. - Lessons from animal models-"japanese Circulation Journal. 64. 1-12 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimokawa H.: "Molecular Mechanisms of Smooth Muscle Contraction,"R. G. Landes Co.. 107-117 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukumoto, Y., Shimokawa H., et al.: "Vasculoprotecvite role of inducible nitric oxide synthase at inflammatory coronary lesions induced by chronic treatment with interleukin-1β in pigs in vivo"Circulation. 96. 3104-3111 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tashiro H., Shimokawa H., et al.: "Altered plasma levels of cytokines in patients with ischemic heart disease"Coronary Artery Disease. 8. 143-147 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Katsumata N., Shimokawa H., et al.: "Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1β"Circulation. 96. 4357-4363 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyata K., Shimokawa H., et al.: "Endothelial vasodilator function is preserved at the spastic/inflammatory coronary lesions in pigs"Circulation. 100. 1432-1437 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimokawa H., Seto M., et al.: "Rho-kinase-mediated pathway induced enhanced myosin light chain phosphrylations in a swine model of coronary artery spasm"Cardiovascular Research. 43. 1029-1039 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimokawa H.: "Cellular and molecular mechanisms of coronary artery spasm -Lessons form animal models-"Japanese Circulation Journal. 64. 1-12 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimokawa H.: "Intracellular mechanisms for coronary artery spasm. In Kohama K, Sasaki Y (eds) : Molecular Mechanisms of Smooth Muscle Contraction"R. G. Landes Co.. 107-117 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fukumoto Y, Shimokawa H, et al.: "Vasculoprotective role of inducible nitric oxide synthase at inflammatory coronary lesions induced by chronic treatment with interleukin-1β in pigs in vivo."Circulation. 96. 3104-3111 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tashiro H, Shimokawa H, et al.: "Altered plasma levels of cytokines in patients with inschemic heart disease."Coronary Artery Disease. 8. 143-147 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Katsumata N, Shimokawa H, et al.: "Enhanced myosin light chain phosphoryla-tions as a central mechanism for coronary artery spasm in a swine model with interleukin-1β"Circulation. 96. 4357-4363 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyata K, Shimokawa H, et al.: "Endothelial vasodilator function is preserved at the spatic/inflammatory coronary lesions in pigs."Circulation. 100. 1432-1437 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimokawa H, Seto M, et al.: "Rho-kinase-mediated pathway induces enhanced myosin light chain phosphorylations in a swine model of coronary artery spasm."Cardiovascular Research. 43. 1029-1039 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimokawa H.: "Cellular and molecular mechanisms of coronary artery spasm.-Lessons from animal models-"japanese Circulation Jouranl. 64. 1-12 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimokawa H.: "Molecular mechanisms of Smooth Muscle Contraction."R.. G. Landes Co.. 107-117 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Oyama J et al.: "Role of nitric oxide and paroxynitrite in the cytokine-induced myocardial dysfunction in dogs in vivo." Journal of Clinical Investigation. 101. 2207-2214 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamawaki T et al.: "Intramural delivery of a specific tyrosine kinase inhibitor with biodegradable stent suppresses the restenotic changes of the coronary artery in pigs in vivo." Journal of American COllege of Caediology. 30. 780-786 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Momii H et al.: "Inhibition of adhesion molecules markedly amiliorates cytokine-indrced sustained myocardial dysfunction in dogs in vivo." Journal of Molecular and Cellular Cardiology. 30. 2637-2650 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimokawa H.: "Intracellular mechanisms for coronary artery spasm." R.G.Randes Co(in press),

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukumoto et al.: "Tyrosine kinase inhibitor suppresses the(re)stenotic changes of the coronary artery after balloon injury in pigs." Cardiovasc Res.32. 1131-1140 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukumoto et al.: "Inflammatory cytokines cause coronary arteriosclerosis-like changes and alterations in the smooth muscle phenotypes in pigs." J Cardiovasc Pharmacol.29. 222-231 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kozai et al.: "Tyrosine kinase inhibitor markedly suppresses the development of coronary lesions induced by chronic treatment with platelet-derived growth factor in pigs in vivo." J Cardiovasc Pharmacol.29. 536-545 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukumoto et al.: "Vasculoprotective role of inducible nitric oxide synthase at inflammatory coronary lesions induced by chronic treatment with interleukin-lb in pigs in vivo." Circulation.96. 3104-3111 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kozai et al.: "Platelet activating factor causes hyperconstriction at the inflammatory coronary lesions in pigs in vivo." Coronary Artery Dis.8. 423-432 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Katsumata et al.: "Enhanced myosin phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-lb." Circulation. 96. 4357-4363 (1997)

    • Related Report
      1997 Annual Research Report

URL: 

Published: 1997-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi