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Elucidation of Molecular Biological Mechanisms for Angiogenic Proliferative Action of Heparin

Research Project

Project/Area Number 07670777
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

FUJITA Masatoshi  Kyoto University, College of Medical Technology, Professor, 医療技術短期大学部, 教授 (50190046)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Kishiko  Kyoto University, College of Medical Technology, Research Associate, 医療技術短期大学部, 助手 (20115900)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsbasic FGF / VEGF / Angiogenesis / Unstable angina / Pericardial fluids / HSP 70 / Chaperone / Collaterals / Smooth muscle cell / ELISA / Intemal mammary artery
Research Abstract

Last year, we evidenced and reported that angiogenic growth factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were produced and released from cardiac tissue, being accumulated in pericardial fluid, and that the concentrations of these growth factors in pericardial fluid from ischemic myocardium were increased, which might contribute to collateral development. This year, we studied whether VEGF and bFGF are released from the heart in response to myocardial ischemia into the pericardial space. The level of VEGF in pericardial fluid was increased only in patients with severe rest angina within 2 days before emergency CABG,while bFGF was increased in all patients undergoing CABG for coronary artery disease. We also evaluated whether HSP 70 acts as a chaperone for the release of bFGF not having the signal sequence. The levels of HSP 70 in pericardial fluid of the patients with unstable angina was twofold higher than that of those with non-ischemic heart disease. Subsequently, we examined the effect of the intramyocardial administration of bFGF combined with gelatin on the development of collateral vessels in dogs with acute coronary occlusion. The dogs treated with control-released bFGF had well-developed collaterals compared with placebo-treated dogs. We concluded that the local sustained delivery of angiogenic growth factors successfully accelerated and potentiated the development of collateral vessels.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Fujita M, et al.: "Prospective, randomized, placebo-controlled, double-blind, multicenter study of exercise with enoxapain pretreatment for stable-effort angina." American Heart Journal. 129. 535-541 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakae I, et al: "Relation between preexistent coronary collateral circulation and the incidence of restenosis after successful primary coronary angioplasty for acute myocardial infarction." Journal of American College of Cardiology. 27. 1688-1692 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M, et al.: "Elevated basic fibroblast growth factor in pericardial fluid of patients with unstable angina." Circulation. 94. 610-613 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M, et al.: "Fate of collaterals after successful coronary angioplasty in patients with effort angina." Journal of American College of Cardiology. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M: "Salutary effects of myocardial ischemia in coronary artery disease." International Journal of Cardiology. 52. 197-202 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shioji K, et al: "Heparin exercise treatment for a patient with arteriosclerosis obliterans." Japanese Circulation Journal. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 藤田正俊(単著): "冠側副血行循環:ヘパリン運動療法の生まれるまで" 中山書店, 98 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 藤田正俊(共著): "狭心病" 医療ジャーナル社, 385 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M,et al.: "Prospective, randomized, plaebo-controlled, double-blind, multicenter study of exercise with enoxaparin pretreatment for stable-effort angina." American Heart Journal. 129. 535-541 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakae I,et al.: "Relation between preexistent coronary collateral circulation and the incidence of restenosis after successful primary coronary angioplasty for acute myocardial infarction." Journal of American College of Cardiology. 27. 1688-1692 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M,et al.: "Elevated basic fibroblast growth factor in pericardial fluid of patients with unstable angina." Circulation. 94. 610-613 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M,et al.: "Fate of collaterals after successful coronary angioplasty in patients with effort angina." Journal of American College of Cardiology. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M: "Salutary effects of myocardial ischemia in coronary artery disease." International Journal of Cardiology. 52. 197-202 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shioji K,et al.: "Heparin exercise treatment for a patient with arteriosclerosis obliterans." Japanese Circulation Journal. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M: Coronary collateral circulation ; until the birth of heparin exercise teratment.Nakayama-Shoten Co., Ltd., 1-98 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M: Angina pectoris ; ed.by Sasayama S.Iyaku Journal Co., Ltd., 1-385 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujita M,et al.: "Prospective,randomized,placebo-controlled,double-blind,multicenter study of exercise with enoxaparin pretreatment for stable-effort angina." American Heart Journal. 129. 535-541 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakae I,et al: "Relation between preexistent coronary collateral circulation and the incidence of restenosis after successful primary coronary angioplasty for acute myocardial infarction." Journal of American College of Cardiology. 27. 1688-1692 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujita M,et al.: "Elevated basic fibroblast growth factor in pericardial fluid of patients with unstable angina." Circulation. 94. 610-613 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujita M,et al.: "Fate of collaterals after successful coronary angioplasty in patients with effort angina." Journal of American College of Cardiology. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujita M: "Salutary effects of myocardial ischemia in coronary artery disease." International Journal of Cardiology. 52. 197-202 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shioji K,et al.: "Heparin exercise treatment for a patient with arteriosclerosis obliterans." Japanese Circulation Journal. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 藤田正俊(単著): "冠側副血行循環:ヘパリン運動療法の生まれるまで" 中山書店, 98 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 藤田正俊(共著): "狭心症" 医薬ジャーナル社, 385 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujita M, et al.: "Prospective, randomized, placebo-controlled, double-blind, multicenter study of exercise with enoxaparin pretreatment for stable-effort angina." American Heart Journal. 129. 535-541 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Miwa K, et al.: "Susceptibility of plasma low density lipoprotein to cupric ion-induced peroxidation in patients with variant angina." Journal of American College of Cardiology. 26. 632-638 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujita M: "Salutary effects of myocardial ischemia in coronary artery disease." International Journal of Cardiology. 52. 197-202 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tanaka T, et al.: "Responses of internal mammary artery local administration of acetylcholine." The American Journal of Cardiology. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hata T, et al.: "Noninvasive assessment of myocardial viability by positron emission tomography with carbon-11 acetate in patients with old myocardial infarction: usefulness of low dose dobutamine infusion." Circulation. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakae I, et al.: "Relationship between the preexistent coronary collateral circulation and the incidence of restenosis following successful primary percutaneous transluminal coronary angioplasty for acute myocardial infarction." Journal of American College of Cardiology. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 藤田正俊(単著): "冠側副血行環境:ヘパリン運動療法の生まれるまで" 中山書店, 98 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 藤田正俊(共著): "狭心症" 医薬ジャーナル社, 385 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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