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Regulation of Expression of Thrombomodulin on the Cultured Human Umbilical Vein Endothelila Cells and Pathomechanism of Thrombosis

Research Project

Project/Area Number 04454574
Research Category

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

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionKAGOSHIMA UNIVERSITY

Principal Investigator

MARUYAMA Ikuro  Kagoshima University School of Medicine, Laboratory Medicine, Professor, 医学部, 教授 (20082282)

Co-Investigator(Kenkyū-buntansha) SHINMYOUZU Kohichi  Kagoshima University School of Medicine, Department of Transfusion Medicine, Ins, 医学部・付属病院, 講師 (20183410)
YONEZAWA Suguru  Kagoshima University School of Medicine, Department of Pathology, Associate Prof, 医学部, 助教授 (10175002)
OSAME Mitsuhiro  Kagoshima University School of Medicine, Department of Internal Medicine, Profes, 医学部, 教授 (10041435)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsThrombomodulin / Cultured Endothelilal Cells / Thrombin Receptor / Vascular Smooth Nusle Cells / Coronary Artery / Coronary Artery Thrombosis / 冠動脈血栓〓 / Thrombomodulin / endothelium / トロンビン / 腎系球体 / 膠原病
Research Abstract

We investigated on 1) regulatrory mechanisims of the expression and dynamics of thrombin receptor (TR) and thrombomodulin (TM), 2) factors which regulate the expression of these receptors, 3) establishment of assay method of TR released peptide (TRRP) upon thrombin activation, 4) signal transduction of thrombin through TR,5) total evaluation method of TM/protein C-protein S natural anticoagulant system.
As results, we obtained as follows :
1) TM is doun-regulated by the stimulation with various stimulus and this is accompanied with increment in TR.
2) Oxdized LDL and advanced glycation endoproducts down-regulated the expression of TM suggesting that these factors act as risk factors not only for atherosclerosis but also for thrombosis.
3) We succeeded the establishment of assay method of TRRP in serum. This peptide was increased in the serum from diabetes melitus patients with vascular complications.
4) Thrombin activates TR receptor and results the activation of NF kappaB.This may be a main pathway in cellular events upon thrombin stimulation.
5) We established the new test for evaluation of TM/protein C and protein S natural anticoagulant system in vitro. We measured prothrombinase inhibition rate by recombinat TM added to the plasma. Resistant for rTM was observed about 15-30% patients with collagen diseases, myocardial infarction, vasulitis syndrome, cerebral infarction.
Based on these data, oxidized LDL and glycated proteins may down-regulate TM with the increment in TR and act as prothrombotic factors. Thus signal transduction of thrombin through TR may result proliferation and thrombosis. This prothrombotic state is detected in part by the assessment of TRRP of TM resistance.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Y.Maruyama,I.Maruyama,et al.: "Thrombin receptor agonist peptide decreases thrombomodulin activity in cultured human umbilical vein endothelial cells" Biochem.Biophys.Res.Commun.199. 1262-1269 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nakajima,I.Maruyama: "Involvement of NF-κB activation in thrombin-induced human vascular smooth muscle cell proliferation." Bichem.Biophys.Res.Commun.204. 950-955 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Nakajima,I.Maruyama: "E5510 antagonizcs thrombin receptor signals by inhibiting NF-κB activation." Biochem.Biophys.Res.Commun.203. 1181-1187 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Aoki,I.Maruyama: "Antithrombotic effects of recombinant human soluble thrombomodulin(rhs-TM)on arteriovenous shunt thrombosis in rats" Am.J.Hematol.47. 162-166 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.Kishida,I.Maruyama,et al.: "Immobilization of human thrombomodulin onto(ether urethane urea)for dveloping antithrombohgenic blood-contacting materials." Biomaterials. 15. 848-852 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Abe,I.Maruyama,et al.: "Increased heparin-releasable platclet factor 4 and D dimer in patients one month after onset of acute myocardial infarction:persistent activation of platelets and the coagulation/fibrinolysis." Int.J.Cardiol.47. S7-S12 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Maruyama, Y., Maruyama, I.& Soejima, Y.: "Thrombin receptor agonist peptide decreases thrombomodulin activity in cultured human umbilical vein endothelial cells" Biochem.Biophys. Res.Commun.199. 1262-1269 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakajima, T., Kitajima, I., Shin., H., Takasaki, I., Shigeta, K., Abeyama, K., Yamashita, Y., Tokoka, T., Soejima, Y.& Maruyama, I.: "Involvement of NFkappaB activation in thrombin-induced human vascular smooth muscle cell prolifration." Biochem.Biophys.Res.Commun. 204. 950-955 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakajima, T., Kitajima, I., Shin., H., Matsumoto, W., Soejima, Y.&Maruyama, I: "E5510 antagonizes thrombin receptor signals by inhibiting NF-kappaB activation" Biochem.Biophys.Res.Commun.203. 1181-1187 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Aoki, Y., Takei, R., Mohri, M., Gonda, Y.Gomi, K., Sugihara, T., Kiyota, T., Yamamoto, S., Ishida, T & Maruyama, I.: "Antithrombotic effcts of recombinant human soluble thrombomodulin (rhs-TM) on arteriovenous shunt thrombosis in rats." Am.J.Hematol. 47. 162-166 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kishida, A., Ueno, Y., Fukudome, N., Yashima, E., Maruyama, I., & Akashi, M.: "Immobilization of human thrombomdulin onto (ether urethane urea) for developing antithrombohgenic blood-contacting materials." Biomaterials. 15. 848-852 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Abe., S., Maruyama, I., Arima, S., Yamaguchi, H., Okino, H., Hamasaki, S., Yamashita, T., Nomoto, K., Tahara, M., AtSuchi, Y., Nakao, S., & Tanaka, H: "Increased heparin-releasable platelet factor 4 and D dimer in patients one month after onset of acute myocardial infarction : persistent activation of platelets and the coagulation/fibrinolysis." Int.J.Cardiol.47. S7-S12 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Maruyama,I.Maruyama,et al.: "Thrombin receptor agonist peptide decreases thrombomodulin activity in cultured human umbilical vein endothelial cells" Biochem.Biophys.Res.Commun.199. 1262-1269 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Nakajima,I.Maruyama: "Involvement of NF-κB activation in thrombin-induced human vascular smooth muscle cell proliferation." Biochem.Biophys.Res.Commun.204. 950-955 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Nakajima,I.Maruyama: "E5510 antagonizes thrombin receptor signals by inhibiting NF-κB activation." Biochem.Biophys.Res.Commun.203. 1181-1187 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Aoki,I.Maruyama: "Antithrombotic effects of recombinant human soluble thrombomodulin(rhs-TM)on arteriovenous shunt thrombosis in rats" Am.J.Hematol.47. 162-166 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] A.Kishida,I.Maruyama,et al.: "Immobilization of human thrombomodulin onto(ether urethane urea)for developing antithrombohgenic blood-contacting materials." Biomaterials. 15. 848-852 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Abe,I.Maruyama,et al.: "Increased heparin-releasable platelet factor 4 and D dimer in patients one month after onset of acute myocardial infarction:persistent activation of platelets and the coagulation fibrinolysis." Int.J.Cardiol.47. S7-S12 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Furuzono: "A novel biomaterial:Poly(dimethylsiloxane)-polyamide multiblock copolymer L Synthesis and evaluation of blood compatibility" J.Biomater.Sci.5. 89-98 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] E.Ikeda: "Expression of thrombomodulin in patients with spontaneous occlusion of the circle of willis" Stroke. 24. 657-660 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Mizutani: "Glomerular localization of thrombomodulin in human glomerulonephritis" Lab.Invest.69. 193-202 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Aritomi: "Recombinant human soluble thrombomodulin delivers bounded thrombin to antithrombin III:Thrombomodulin associates with free thrombin and is recycled to activate protein C" Thromb.Haemost.70. 418-422 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] R.Ohishi: "Evidence that the protein C activation pathway amplifies the inhibition of thrombin generation by recombinant human thrombomodulin in plasma" Thromb.Haemost.70. 423-426 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Gonda: "Antithrombotic effect of recombinant human soluble thrombomodulin on endotoxin-induced disseminated intravascular coagulation in rats" Thromb.Res.71. 325-335 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Nakajima: "Overgrowth of human synovial cells driven by the human T cell leukemia virus type I tax gene" J.Clin.Invest.92. 186-193 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] I.Maruyama: "Vesnarinone inhibits production of HIV-1 in cultured cells" B.B.R.C.195. 1264-1271 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masashi Ueyama,Ikuro Maruyama,Mitsuhiro Osame,Yusuke Sawada: "Marked increase in plasma interleukin-6 in burn patients." J.Lab.Clin.Med.120. 693-698 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ikuro Maruyama: "Endothelial anticoagulant-Its structure,function and expression." J.Circ.J.88. 115-119 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mitsuru Akashi,Ikuro Maruyama,Norihiro Fukudome,Eiji Yashima: "Immobilization of human thrombomodulin of glass beads and its anticoagulant activity." Bioconjugate Chem.3. 363-365 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 丸山 征郎: "血小板の構造と機能ーこの不思議な細胞の今日的理解ー" ファーマインターナショナル, 89 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ikuro Maruyama,Mitsuru Akashi,Tadashi Okadome: "Hemostasis and Circulation." Springer-Verlarg Press., 212 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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