1994 Fiscal Year Final Research Report Summary
Regulation of Expression of Thrombomodulin on the Cultured Human Umbilical Vein Endothelila Cells and Pathomechanism of Thrombosis
| Project/Area Number |
04454574
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | KAGOSHIMA UNIVERSITY |
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Principal Investigator |
MARUYAMA Ikuro Kagoshima University School of Medicine, Laboratory Medicine, Professor, 医学部, 教授 (20082282)
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| 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)
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| Project Period (FY) |
1992 – 1994
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| Keywords | Thrombomodulin / Cultured Endothelilal Cells / Thrombin Receptor / Vascular Smooth Nusle Cells / Coronary Artery / Coronary Artery Thrombosis |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
