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The mechanism of antithrombotic properties of statins; New insight to its therapeutic potential for the prevention of thrombotic diseases.

Research Project

Project/Area Number 15K19176
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Laboratory medicine
Research InstitutionKanazawa University

Principal Investigator

SEKIYA Akiko  金沢大学, 保健学系, 助教 (10452111)

Research Collaborator MORISHITA eriko  
MARUYAMA keiko  
ASAKURA hidesaku  
OHTAKE shigeki  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsHMG-CoA還元酵素阻害剤(スタチン) / TFPI / ADAMTS13 / 抗血栓療法 / スタチン / 血栓
Outline of Final Research Achievements

The aim of this study was to investigate the mechanism of how HMG-CoA reductase inhibitors (statins) play a role of antithrombotic properties. In our in-vitro experiments, fluvastatin increased tissue factor pathway inhibitor (TFPI) expression in human umbilical vein endothelial cells. Fluvastatin also increased a disintegrin and metalloproteinase with a thrombosponsin type 1 motif, menber 13 (ADAMTS13) expression in human hepatic stellate cells. Both TFPI and ADAMTS13 play crucial roles in inhibition of thrombus formation. This study revealed unknown mechanisms of the anticoagulant effect of statins and gave a new insight to its therapeutic potential for the prevention of thrombotic diseases.

Academic Significance and Societal Importance of the Research Achievements

スタチンには、抗血栓作用もあることが知られているが、その機序については不明な点が多かった。スタチンはコレステロール低下薬として既に臨床で広く用いられており、出血リスクを増大しないことが立証されていることから、スタチンを抗血栓療法に用いることへの期待度は高いといえる。また、本研究の「抗血栓作用」の機構に特異的に作動する薬剤を開発できれば、それはまさに「出血リスクを増大しない理想的な抗血栓薬」となる可能性がある。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 7 results,  Acknowledgement Compliant: 6 results) Presentation (18 results) (of which Invited: 1 results)

  • [Journal Article] Gene analysis of inherited antithrombin deficiency and functional analysis of abnormal antithrombin protein (N87D)2018

    • Author(s)
      Kamijima S, Sekiya A, Takata M, Nakano H, Murakami M, Nakazato T, Asakura H, Morishita E
    • Journal Title

      Int J Hematol

      Volume: 107 Issue: 4 Pages: 490-494

    • DOI

      10.1007/s12185-017-2352-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thrombosis Prediction Based on Reference Ranges of Coagulation-Related Markers in Different Stages of Pregnancy.2017

    • Author(s)
      Sekiya A, Hayashi T, Kadohira Y, Shibayama M, Tsuda T, Jin X, Nomoto H, Asakura H, Wada T, Ohtake S, Morishita E
    • Journal Title

      Clin Appl Thromb Hemost

      Volume: 印刷中 Issue: 7 Pages: 844-850

    • DOI

      10.1177/1076029616673732

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Causative genetic mutations for antithrombin deficiency and their clinical background among Japanese patients.2017

    • Author(s)
      Sekiya A, Taniguchi F, Yamaguchi D, Kamijima S, Kaneko S, Katsu S, Hanamura M, Takata M, Nakano H, Asakura H, Ohtake S, Morishita E
    • Journal Title

      Int J Hematol

      Volume: 105 Issue: 3 Pages: 287-294

    • DOI

      10.1007/s12185-016-2142-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gene analysis of six cases of congenital protein S deficiency and functional analysis of protein S mutations (A139V, C449F, R451Q, C475F, A525V and D599TfsTer13)2017

    • Author(s)
      Taniguchi F, Morishita E, Sekiya A, Nomoto H, Katsu S, Kaneko S, Asakura H, Ohtake S
    • Journal Title

      Thromb Res

      Volume: 151 Pages: 8-16

    • DOI

      10.1016/j.thromres.2016.12.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] ELISAによる抗リン脂質抗体価測定の標準化に向けて2016

    • Author(s)
      本木 由香里,野島 順三,吉田 美香,關谷 暁子,原 和冴,森下 英理子,家子 正裕
    • Journal Title

      日本血栓止血学会誌

      Volume: 27 Issue: 6 Pages: 644-652

    • DOI

      10.2491/jjsth.27.644

    • NAID

      130005250257

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Fluvastatin Upregulates the Expression of Tissue Factor Pathway Inhibitor in Human Umbilical Vein Endothelial Cells2015

    • Author(s)
      Sekiya A, Morishita E, Maruyama K, Torishima H, Ohtake S.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 22 Issue: 7 Pages: 660-668

    • DOI

      10.5551/jat.28175

    • NAID

      130005089136

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ELISA-based detection system for protein S K196E mutation, a genetic risk factor for venous thromboembolism2015

    • Author(s)
      Maruyama K, Akiyama M, Kokame K, Sekiya A, Morishita E, Miyata T
    • Journal Title

      PLoS One

      Volume: 10 Issue: 7 Pages: e0133196-e0133196

    • DOI

      10.1371/journal.pone.0133196

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Late onset thrombosis in two Japanese patients with compound heterozygote protein S deficiency.2015

    • Author(s)
      Taniguchi F, Morishita E, Sekiya A, Yamaguchi D, Nomoto H, Kobayashi E, Takata M, Kosugi I, Takeuchi N, Asakura H, Ohtake S.
    • Journal Title

      Thromb Res

      Volume: in press Issue: 6 Pages: 1221-1223

    • DOI

      10.1016/j.thromres.2015.03.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] EliAによる自動分析装置を用いた抗リン脂質抗体価測定の有用性2017

    • Author(s)
      本木由香里,吉田美香,關谷暁子,原 和冴,家子正裕,森下英理子,野島順三
    • Organizer
      第18回日本検査血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 当研究室で解析した先天性アンチトロンビン(AT)・プロテインC(PC)・プロテインS(PS)欠損症の遺伝子解析ならびに所見2017

    • Author(s)
      村上森花,中野明華,上島沙耶香,關谷暁子,森下英理子
    • Organizer
      第42回北陸臨床病理集談会
    • Related Report
      2017 Research-status Report
  • [Presentation] 先天性プロテインC欠損症の遺伝子解析および異常プロテインC蛋白(K437E)の機能解析2017

    • Author(s)
      上島沙耶香,宮崎香織,關谷暁子,村上森花,中野明華,森下英理子
    • Organizer
      第42回北陸臨床病理集談会
    • Related Report
      2017 Research-status Report
  • [Presentation] 直接経口抗凝固薬が血中アンチトロンビン、プロテインC、プロテインS活性測定値に与える影響2017

    • Author(s)
      寺上貴子,森下英理子,關谷暁子,森三佳,林研至,末武司,鈴木健史,小濱聖佳,古荘浩司,朝倉英策,和田隆志
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 先天性血栓性素因の病態とその解釈2017

    • Author(s)
      關谷暁子,森下英理子,朝倉英策
    • Organizer
      第18回日本検査血液学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 抗凝固療法が先天性凝固異常のスクリーニング検査に与える影響2016

    • Author(s)
      金森尚美,古荘浩司,關谷暁子,高島伸一郎,加藤武史,村井久純,薄井荘一郎,林研至,森下英理子,高村雅之
    • Organizer
      第64回日本心臓病学会学術集会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
  • [Presentation] プロテインS比活性によるプロテインS異常症のスクリーニング2016

    • Author(s)
      金秀日, 津田友秀, 森下英理子, 關谷暁子, 康東天, 濱崎直孝
    • Organizer
      第48回日本臨床検査自動化学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-09-22
    • Related Report
      2016 Research-status Report
  • [Presentation] 学生と現役技師が抱く「良い臨床検査技師」像の比較2016

    • Author(s)
      關谷暁子,長原三輝雄,岡本成史,葭谷愛子,和田隆志,大竹茂樹,櫻井博,稲津明広
    • Organizer
      第11回日本臨床検査学教育学会学術大会
    • Place of Presentation
      神戸常盤大学(兵庫県神戸市)
    • Year and Date
      2016-08-31
    • Related Report
      2016 Research-status Report
  • [Presentation] 直接経口抗凝固薬が血中アンチトロンビン、プロテインC、プロテインS活性値に与える影響2016

    • Author(s)
      關谷暁子,鈴木健史,三澤絵梨,末武 司,古荘浩司,林研至,朝倉英策,大竹茂樹,森下英理子
    • Organizer
      第17回日本検査血液学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-08-06
    • Related Report
      2016 Research-status Report
  • [Presentation] 抗リン脂質抗体価測定ELISAの標準化に向けた取組み2016

    • Author(s)
      本木由香里,吉田美香,關谷暁子,原 和冴,家子正裕,森下英理子,野島順三
    • Organizer
      第17回日本検査血液学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-08-06
    • Related Report
      2016 Research-status Report
  • [Presentation] 先天性AT欠乏症24家系の臨床所見ならびに遺伝子変異部位の検討2016

    • Author(s)
      勝詩織,關谷暁子,金子将ノ助,朝倉英策,大竹茂樹,森下英理子
    • Organizer
      第38回日本血栓止血学会学術集会
    • Place of Presentation
      奈良春日野国際フォーラム甍(奈良県奈良市)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] リバーロキサバンが血中アンチトロンビン,プロテインC,プロテインS活性値に与える影響および試薬間比較2016

    • Author(s)
      關谷暁子,三澤絵梨,鈴木健史,末武司,津田友秀,金秀日,古荘浩司,林研至,朝倉英策,森下英理子
    • Organizer
      第10回日本血栓止血学会学術標準化委員会シンポジウム
    • Place of Presentation
      野村コンファレンスプラザ日本橋(東京都中央区)
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
  • [Presentation] Influences of rivaroxaban on laboratory data of antithrombin,protein C and protein S activities2015

    • Author(s)
      Akiko Sekiya, Eri Misawa, Takesi Suzuki, Nobuo Arai, Hirosi Furusho, Kenshi Hayashi, Hidesaku Asakura, Shigeki Ohtake, Eriko Morishita
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      石川県立音楽堂ほか(石川県金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] A congenital dysprothrombinemia with both decreased prothrombin activity and antithrombin resistance2015

    • Author(s)
      Mao Takata, Eriko Morishita,Fumina Taniguchi, Akiko Sekiya,Erina Kobayashi, Hidesaku Asakura,Akira Takagi,Tetsuhiro kojima, Shigeki Ohtake
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      石川県立音楽堂ほか(石川県金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Detection of protein S K196E mutation by a newly developed ELISA-based system2015

    • Author(s)
      Erina Kobayashi, Fumina Taniguchi,Keiko Maruyama, Mao Takata,Shiori Katsu,Shonosuke Kaneko, Akiko Sekiya, Shigeki Ohtake,Toshiyuki Miyata, Eriko Morishita
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      石川県立音楽堂ほか(石川県金沢市)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] リバーロキサバン使用例における,プロテインS活性値の試薬間比較2015

    • Author(s)
      關谷暁子,三澤絵梨,鈴木健史,新井信夫,津田友秀,金秀日,古荘浩司,林研至,大竹茂樹,森下英理子
    • Organizer
      第16回日本検査血液学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-07-11
    • Related Report
      2015 Research-status Report
  • [Presentation] プロテインCK193del変異検出のためのPC活性測定法の検討2015

    • Author(s)
      高田麻央,關谷暁子,小林英里奈,野本明華,朝倉英策,大竹茂樹,森下英理子
    • Organizer
      第16回日本検査血液学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-07-11
    • Related Report
      2015 Research-status Report
  • [Presentation] ワルファリンのプロテインS,プロテインC測定値への影響2015

    • Author(s)
      小林英里奈,關谷暁子,三澤絵梨,鈴木健史,新井信夫,高田麻央,野本明華,朝倉英策,大竹茂樹,森下英理子
    • Organizer
      第16回日本検査血液学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-07-11
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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