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Study on the prediction of thrombosis formation during exercise

Research Project

Project/Area Number 15500455
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Sports science
Research InstitutionNara Medical University

Principal Investigator

ISHIZASHI Hiromichi  Nara Medical University, Faculty of Medicine, Assistant Professor, 保健体育学, 講師 (50260807)

Co-Investigator(Kenkyū-buntansha) 松本 雅則  奈良県立医科大学, 輸血部, 助手 (60316081)
藤村 吉博  奈良県立医科大学, 輸血部, 教授 (80118033)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsVWF / UL-VWFM / ADAMTS13 / hard exercise / mild exercise / sweating / dehydration / thrombi formation / VWF-CPass / 運動負荷 / 水分摂取 / vWF / Ul-vWFM / vWF-CPase
Research Abstract

von Willebrand factor(VWF) is synthesized in vascular endothelial cells, and released into the plasma as "unusually large" VWF multimers(UL-VWFM), which is degraded by ADAMTS13. Deficiency of ADAMTS13 increases the plasma levels of UL-VWFM, which leads to platelet clumping and/or thrombi formation. VWF antigen(VWF:Ag) in plasma was reported to increase during exercise, but the dynamics on VWT and its degradation on exercise has not been clarified. In order to clarify their homeostatic modulation in vivo, we measured platelet count and plasma values of VWF:Ag, UL-VWFM, ristocetin cofactor(RCof) and ADAMTS13 before and after exercise for 12 hours in 20 healthy male volunteers. Two types of exercise was applied using bicycle ergometer as follows ; 65% VO2 max for 1 hour (hard exercise) and 40% VO2 max for 1 four (mild exercise). As a result, immediately after hard exercise, VWF:Ag and RCof significantly increased, and UL-VWFM was detected, and lasted for 6 hours and disappeared in 12 hour … More s. In contrast, after mild exercise, the increase in VWF was not observed. ADAMTS13 significantly decreased 2 hours after hard exercise and gradually recovered within 5 hours. These findings suggest that the increase in UL-VWFM after hard exercise is due to the compensatory phenomenon to prevent the excessive bleeding at trauma caused by exercise-induced hypertension, followed by the consumption of ADAMTS13 to degrade increased amounts of UL-VWFM. Furthermore, we evaluated the relationship of VWF:antigen to dehydration during exercise because of sweating. As a result, RCof after hard exercise tended to be positively correlated with the degree of sweating per body weight, supporting that the degree of dehydration is closely related to the ability of VWF-dependent platelet aggregation during exercise. These results suggest that enough amount of water intake will be necessary to obtain early physiological response to decrease the platelet aggregation and subsequent occurrence of thrombi formation in small vessels at the recovery phase after exercise. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 2003 Other

All Journal Article (15 results) Publications (6 results)

  • [Journal Article] Development of ADAMTS13 inhibitor in a patient with hepatitis C virus-related liver cirrhosis causes thrombotic thrombocytopenic purpura.2005

    • Author(s)
      Yagita M, Ishizashi H, 他9名
    • Journal Title

      J.Hepatology 42

      Pages: 420-421

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adenovirus-mediated transfer of human placental ecto-ATP diphosphohydrolase I to vascular smooth muscle cells suppresses platelet aggregation in vitro and arterial thrombus formation in vivo.2005

    • Author(s)
      Furukoji, Matsumoto M, 他9名
    • Journal Title

      Circulation 111

      Pages: 808-815

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The Japanese experience with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.2004

    • Author(s)
      Matsumoto M, Yagi H, Ishizashi H, Wada H, Fujimura Y.
    • Journal Title

      Semin Hematol 41

      Pages: 68-74

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome.2004

    • Author(s)
      Matsumoto M, Ishizashi H.他16名
    • Journal Title

      Blood 103

      Pages: 1305-1310

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13.2004

    • Author(s)
      Kokame K, Matsumoto M, Fujimura Y, Miyata T.
    • Journal Title

      Blood 103

      Pages: 607-612

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura2004

    • Author(s)
      Uchida T, Matsumoto M, 他11名
    • Journal Title

      Blood 104

      Pages: 2081-2083

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The Japanese experience with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.2004

    • Author(s)
      Matsumoto M, Yagi H, Ishizashi H, Wada H, Fujimura Y.
    • Journal Title

      Seminar in Hematol 41

      Pages: 68-74

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome.2004

    • Author(s)
      Matsumoto M, Kokame K, Soejima K, Miura M, Hayashi S, Fujii Y, Iwai A, Ito E, Tsuji Y, Takada-Shitaka M, Iwadate M, Umeyama H, Yagi H, Ishizashi H, Banno F, Nakagaki T, Miyata T, Fujimura Y.
    • Journal Title

      Blood 103

      Pages: 1305-1310

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura.2004

    • Author(s)
      Uchida T, Wda H, Mizutani M, Iwashita M, Ishihara H, Shibano T, Suzuki M, Matsubara Y, Soejima K, Matsumoto M, Fujimura Y, Ikeda Y, Murata M.
    • Journal Title

      Blood 104

      Pages: 2081-2083

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura.2004

    • Author(s)
      Uchida T, Matsumoto M, 他11名
    • Journal Title

      Blood 104

      Pages: 2081-2083

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Diffuse neurodeficits in intravascular lymphomatosis with ADAMTS13 inhibitor.2004

    • Author(s)
      Kawahara M, Matsumoto M, 他7名
    • Journal Title

      Neurology 63

      Pages: 1731-1733

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ADAMTS-13 cysteine-rich/spacer domains are functionally essential for von Willebrand factor cleavage.2003

    • Author(s)
      Soejima K, Ishizashi H.他8名
    • Journal Title

      Blood 102

      Pages: 3232-3237

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Significance of measuring von Willebrand factor-cleaving protease activity in thrombotic microangiopathy after living donor liver transplantation.2003

    • Author(s)
      Nakazawa Y, Ishizashi H.他9名
    • Journal Title

      Liver Transplant 9

      Pages: 1328-1333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ADAMTS-13 cysteine-rich/spacer domains are functionally essential for von Willebrand factor cleavage.2003

    • Author(s)
      Soejima K, Matsumoto M, Kokame K, Yagi H, Ishizashi H, Maeda H, Nozaki C, Miyata T, Fujimura Y, Nakagaki T.
    • Journal Title

      Blood 102

      Pages: 3232-3237

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Significance of measuring von Willebrand factor-cleaving protease activity in thrombotic microangiopathy after living donor liver transplantation.2003

    • Author(s)
      Nakazawa Y, Hashikura Y, Ogino S, Urata K, Ikegami T, Terada M, Yagi H, Ishizashi H, Matsumoto M, Fujimura Y, Kawasaki S.
    • Journal Title

      Liver Transplant 9

      Pages: 1328-1333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Matsumoto M, et al.: "Molecular characterization of ADAMTS13 gene mutations Japanese patients with Upshaw-Schulman syndrome"Blood. 103. 1305-1310 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsumoto M, et al.: "The Japanese experience with TTP/HUS."Seminars in Hematology. 41. 68-74 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kokame K, et al.: "VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13."Blood. 103. 607-612 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Soejima K, et al.: "ADAMTS-13 cysteine-rich/spacer domains are functionally essential for von Willebrand factor cleavage."Blood. 102. 3232-3237 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakazawa Y, et al.: "von Willebrand factor-cleaving protease activity in thrombotic microangiopathy after living donor liver transplantation."Liver Transplantation. 9. 1328-1333 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugimoto M, et al.: "Mural thrombus generation in type 2A and 2B von Willebrand disease under high shear conditions."Blood. 101. 915-920 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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