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Mechanism of atherosclerosis progression by platelet CLEC-2

Research Project

Project/Area Number 18K06912
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionUniversity of Yamanashi

Principal Investigator

INOUE Osamu  山梨大学, 大学院総合研究部, 特任教授 (00432154)

Co-Investigator(Kenkyū-buntansha) 井上 克枝  山梨大学, 大学院総合研究部, 教授 (10324211)
築地 長治  山梨大学, 大学院総合研究部, 講師 (20710362)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords血小板 / CLEC-2 / podoplanin / 動脈硬化 / メカニズム
Outline of Final Research Achievements

Platelets play a role in progression of atherosclerosis. Podoplanin, which is a ligand for a platelet activation receptor CLEC-2, is expressed on the surface of macrophages infiltrated into atherosclerotic lesion. CLEC-2 depletion inhibited atherosclerotic lesion and macrophage infiltration into the lesion in ApoE-deficient mice fed with high fat diet. These mice also showed increased percentage of monocytes in mononuclear cells and 20-50% of these monocytes bound to platelets. These findings suggest that platelet CLEC-2 binds to PDPN in monocytes, which facilitates monocyte infiltration into the subendothelial lesion and differentiation into macrophages, thereby atherosclerosis is aggravated.

Academic Significance and Societal Importance of the Research Achievements

動脈硬化病変は進行すると脂質に富むプラークとなるが、脆弱なため破綻した場合血栓症を引き起こす。血小板は、プラーク破綻時の血栓形成だけでなく動脈硬化自体の進行にも関与することが知られている。これまでにGPIbに代表されるいくつかの血小板活性化受容体の抗体やノックアウトマウスで動脈硬化進展抑制効果が確認されているが、出血傾向の助長という問題があった。血小板活性化受容体CLEC-2欠損マウスは、病的血栓形成は抑制されるが、出血傾向の有意な増悪は認められない。CLEC-2は、出血傾向のない抗動脈硬化薬剤のターゲット蛋白となりうる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2020 2019 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Journal Article] Role of Platelet C-Type Lectin-Like Receptor 2 in Promoting Lung Metastasis in Osteosarcoma2020

    • Author(s)
      Jiro Ichikawa, Takashi Ando, Tomonori Kawasaki, Tomoyuki Sasaki, Toshiaki Shirai, Nagaharu Tsukiji, Yujiro Kimura, Kaoru Aoki, Keiko Hayakawa, Katsue Suzuki-Inoue, Masao Saitoh, Hirotaka Haro
    • Journal Title

      Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

      Volume: in press Issue: 9 Pages: 1738-1750

    • DOI

      10.1002/jbmr.4045

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Crosstalk between hemostasis and lymphangiogenesis2020

    • Author(s)
      Suzuki‐Inoue Katsue、Tsukiji Nagaharu、Otake Shimon
    • Journal Title

      Journal of Thrombosis and Haemostasis

      Volume: 18 Issue: 4 Pages: 767-770

    • DOI

      10.1111/jth.14726

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelet CLEC‐2 and lung development2020

    • Author(s)
      Suzuki‐Inoue Katsue、Tsukiji Nagaharu
    • Journal Title

      Research and Practice in Thrombosis and Haemostasis

      Volume: 4 Issue: 4 Pages: 481-490

    • DOI

      10.1002/rth2.12338

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Heme Activates Platelets and Exacerbates Rhabdomyolysis-Induced Acute Kidney Injury via CLEC-2 and GPVI/FcRγ2020

    • Author(s)
      S. Oishi, N. Tsukiji, S. Otake, N. Oishi, T. Sasaki, T. Shirai, Y. Yoshikawa, K. Takano, T. Kondo, K. Suzuki-Inoue
    • Organizer
      ISTH 2020 Congress
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血小板受容体CLEC-2による関節リウマチの病態形成への関与2020

    • Author(s)
      佐々木知幸、白井俊光、築地長治、小山賢介、田村彰吾、大竹志門、長田誠、佐藤金夫、波呂浩孝、尾崎由基男、井上克枝
    • Organizer
      第42回日本血栓止血学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 巨核球・血小板上C-type lectin-like receptor 2 (CLEC-2)の赤血球造血における役割2020

    • Author(s)
      大竹志門、白井俊光、築地長治、佐々木知幸、田村彰吾、髙野勝弘、尾崎由基男、井上克枝
    • Organizer
      第42回日本血栓止血学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 横紋筋融解症に併発する腎障害における血小板CLEC-2およびGPVIの役割2020

    • Author(s)
      大石沙織、築地長治、大竹志門、大石直輝、佐々木知幸、白井俊光、吉河佑莉、髙野勝弘、近藤哲夫、井上克枝
    • Organizer
      第42回日本血栓止血学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Platelet C-type Lectin-Like Receptor 2 (CLEC-2) is Required for Optimal Regulation of Erythropoiesis2019

    • Author(s)
      S. Otake, T. Shirai, N. Tsukiji, T. Sasaki, K. Satoh, S. Tamura, K. Takano, Y. Ozaki, K. Suzuki-Inoue
    • Organizer
      第27回国際血栓止血学会学術集会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Heme Induces Platelet Aggregation via Two ITAM Receptors: Implications in Rhabdomyolysis-Induced Acute Kidney Injury2019

    • Author(s)
      N. Tsukiji, S. Oishi, S. Otake, T. Sasaki, K. Takano, K. Suzuki-Inoue
    • Organizer
      第27回国際血栓止血学会学術集会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヘム惹起血小板凝集及び横紋筋融解誘導性急性腎障害における血小板CLEC-2の関与2019

    • Author(s)
      築地長治, 大竹志門, 佐々木知幸, 吉河佑莉, 高野勝弘, 井上克枝
    • Organizer
      第41回日本血栓止血学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 血小板・巨核球上のC型レクチン様受容体(CLEC-2)が、赤血球造血に及ぼす役割2019

    • Author(s)
      大竹志門, 白井俊光, 築地長治, 佐々木知幸, 田村彰吾, 尾崎由基男, 井上克枝
    • Organizer
      第41回日本血栓止血学会学術集会
    • Related Report
      2019 Research-status Report
  • [Remarks] 山梨大学大学院医学工学総合研究部臨床検査医学講座

    • URL

      https://www.med.yamanashi.ac.jp/clinical/clin0lab/

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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