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Regulation of endothelial cell functions by anticoagulant factors and gap junction.

Research Project

Project/Area Number 22790700
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionMie University

Principal Investigator

OKAMOTO Takayuki  三重大学, 大学院・医学系研究科, 助教 (30378286)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords血管内皮細胞 / 活性化プロテインC / トロンボモジュリン / ギャップ結合 / コネキシン / 炎症 / 血液凝固 / 血管新生 / 血管病変 / 内皮細胞
Research Abstract

Cardiovascular diseases, such as atherosclerosis and thromboembolism, are caused by endothelial dysfunctions associated with pathogenic activation of blood coagulation and inflammation. Our goal is to understand the mechanisms for protection and maintenance of endothelial functions. I first investigated the effects of activated protein C and thrombomodulin on endothelial gap junction. My results demonstrated that these factors enhance gap junction intercellular communication. Next, I indicated that inhibition of gap junction protein connexin32 increases tissue factor expression and that overexpression connexin32 enhances tube formation of endothelial cells. In addition, endothelial cells modulate monocyte/neutrophil activation via gap junction mediated cell-cell interaction. These results suggested activated protein C and thrombomodulin regulate gap junction cell-cell interaction in order to maintain endothelial functions and homeostasis.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (27 results)

All 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 7 results) Presentation (13 results) Remarks (1 results)

  • [Journal Article] Thrombomodulin, a bi-functional modulator of inflammation and coagulation in sepsis2011

    • Author(s)
      Okamoto, T., Tanigami, H., Suzuki, K., Shimaoka, M.
    • Journal Title

      Critical Care Research and Practice

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Connexin32 protects against vascular inflammation by modulating inflammatory cytokine expression by endothelial cells2011

    • Author(s)
      Okamoto, T., Akiyama, M., Takeda, M., Akita, N., Yoshida, K., Hayashi, T., Suzuki, K.
    • Journal Title

      Experimental Cell Research

      Volume: 317 Pages: 348-355

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] トロンボモジュリンを介した凝固炎症反応と敗血症性DIC2011

    • Author(s)
      岡本貴行、鈴木宏治
    • Journal Title

      Thrombosis Medcine

      Volume: 11月号

    • Related Report
      2011 Final Research Report
  • [Journal Article] Thrombomodulin, a bi-functional modulator of inflammation and coagulation in sepsis2011

    • Author(s)
      Okamoto T, Suzuki K, et al
    • Journal Title

      Crit Care Res Pract

      Volume: 2012 Pages: 10-10

    • DOI

      10.1155/2012/614545

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] トロンボモジュリンを介した凝固炎症反応と敗血症性DIC2011

    • Author(s)
      岡本貴行、鈴木宏治
    • Journal Title

      Thrombosis Medicine

      Volume: 1 Pages: 170-176

    • Related Report
      2011 Annual Research Report
  • [Journal Article] An in vitro method for screening anti-platelet agents using a microchannel array flow analyzer2010

    • Author(s)
      Kamada, H., Okamoto, T., Hayashi, T., Suzuki, K.
    • Journal Title

      Biorheology

      Volume: 47 Pages: 153-161

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activated protein C stimulates osteoblast proliferation via endothelial protein C receptor2010

    • Author(s)
      Kurata, T., Hayashi, T., Yoshikawa, T., Okamoto, T., Yoshida, K., Iino, T., Uchida, A. and Suzuki, K.
    • Journal Title

      Thrombosis research

      Volume: 125 Pages: 184-191

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] トロンビン受容体2010

    • Author(s)
      岡本貴行、鈴木宏治
    • Journal Title

      International Review of Thrombosis

      Volume: 5 Pages: 200-203

    • Related Report
      2011 Final Research Report
  • [Journal Article] 凝固制御機序2010

    • Author(s)
      岡本貴行、鈴木宏治
    • Journal Title

      救急・集中治療

      Volume: 22 Pages: 1402-1407

    • Related Report
      2011 Final Research Report
  • [Journal Article] An in vitro method for screening anti-platelet agents using a microchannel array flow analyzer.2010

    • Author(s)
      Kamada H., et al.
    • Journal Title

      Biorheology

      Volume: 47 Pages: 153-161

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Connexin32 protects against vascular inflammation by modulating inflammatory cytokine expression by endothelial cells.2010

    • Author(s)
      Okamoto T., et al.
    • Journal Title

      Experimental Cell Research

      Volume: 317 Pages: 348-355

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] トロンビン受容体2010

    • Author(s)
      岡本貴行、鈴木宏治
    • Journal Title

      International Review of Thrombosis(メディカルレビュー社)

      Volume: 5 Pages: 200-203

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 凝固制御機序2010

    • Author(s)
      岡本貴行、鈴木宏治
    • Journal Title

      救急・集中治療DICのすべて(総合医学社)

      Volume: 22 Pages: 1402-1407

    • Related Report
      2010 Annual Research Report
  • [Presentation] Gap junction protein, connexin32 regulates expression of tissue factor and inflammatory cytokines in the endothelial cells2011

    • Author(s)
      Takayuki Okamoto, et al
    • Organizer
      XXIII Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      京都市
    • Year and Date
      2011-07-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Connexin32 regulates pro-coagulant activity of endothelial cells due to modulating tissue factor expression during inflammation2011

    • Author(s)
      Takayuki Okamoto, Tatsuya Hayashi, Koji Suzuki
    • Organizer
      2011 International Gap Junction Conference
    • Place of Presentation
      ゲント大学
    • Related Report
      2011 Final Research Report
  • [Presentation] Gap junction protein, connexin32 regulates expression of tissue factor and inflammatory cytokines in the endothelial cells2011

    • Author(s)
      Takayuki Okamoto, Tatsuya Hayashi, Koji Suzuki
    • Organizer
      XXIII Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of protein C inhibitor on lipopolysaccharide-induced vascular permeability2011

    • Author(s)
      Tomoaki Yoshikawa, Yoshinori Saito, Tatsuya Hayashi, Tatsuya Kurata, Junji Nishioka, Takayuki Okamoto, Nobuyuki Akita, Kunihiro Asanuma, Akihiro Sudo, Atsumasa Uchida
    • Organizer
      XXIII Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Anticoagulant activated protein C suppresses osteoclast differentiation via endothelial protein C receptor2011

    • Author(s)
      Kakunoshin Yoshida, Takayuki Okamoto, Kunihiro Asanuma, Tatsuya Hayashi, Kuji Suzuki, Atsumasa Uchida, Akihiro Sudo
    • Organizer
      XXIII Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of endotoxin and inflammatory cytokines on protein S and C4B-binding expressions in the liver HepG2 cells2011

    • Author(s)
      Tatsuya Hayashi, Chiemi Kato, Takako Mori, Kakunoshin Yoshida, Nobuyuki Akita, Takayuki Okamoto, Junji Nishioka, Koji Suzuki
    • Organizer
      XXIII Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] The inhibition of lung metastasis by inactivation of coagulation activity may lead to dissemination of tumor cells2011

    • Author(s)
      Kunihiro Asanuma, Nobuyuki Akita, Takayuki Okamoto, Tatsuya Hayashi, Tomoaki Yoshikawa, Kakunoshin Yoshida, Yumiko Asanuma, Akihiko Matsumine, Atsumasa Uchida, Akihiro Sudo, Koji Suzuki
    • Organizer
      XXIII Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Protein C inhibitor inhibits tumor cell growth, but promotes tumor cell metastasis by its procoagulant properties in vivo2011

    • Author(s)
      Nobuyuki Akita, Kakunoshin Yoshida, Takayuki Okamoto, Junji Nishioka, Tatsuya Hayashi, Koji Suzuki
    • Organizer
      XXIII Congress of the International Society on Thrombosis and Haemostasis
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Final Research Report
  • [Presentation] Connexin32 regulates pro-coagulant activity of endothelial cells due to modulating tissue factor expression during inflammation2011

    • Author(s)
      Takayuki Okamoto, et al
    • Organizer
      International Gap Junction Conference 2011
    • Place of Presentation
      Ghent, Belgium
    • Related Report
      2011 Annual Research Report
  • [Presentation] ギャップ結合を介した血管内皮細胞間相互作用は炎症と凝固の増幅を制御している2010

    • Author(s)
      岡本貴行、林辰弥、鈴木宏治
    • Organizer
      第33回日本血栓止血学会
    • Place of Presentation
      鹿児島市
    • Year and Date
      2010-04-23
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] コネキシン32が血管内皮細胞の炎症性サイトカイン発現に及ぼす影響2010

    • Author(s)
      岡本貴行、林辰弥、鈴木宏治
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      日神戸市
    • Related Report
      2011 Final Research Report
  • [Presentation] Connexin32, a gap junction protein, modulates inflammatory cytokine expression in vascular endothelial cells2010

    • Author(s)
      Takayuki Okamoto, Tatsuya Hayashi, Koji Suzuki
    • Organizer
      The 6th Asia Pacific Society on Thrombosis and Hemostasis Congress
    • Place of Presentation
      インドネシア
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] コネキシン32が血管内皮細胞の炎症性サイトカイン発現に及ぼす影響2010

    • Author(s)
      岡本貴行、林辰弥、鈴木宏治
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
    • Place of Presentation
      神戸市
    • Related Report
      2010 Annual Research Report
  • [Remarks] 現在、準備中です

    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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