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

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790700
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Mie 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
• 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

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.

Research Products

• [Journal Article] Thrombomodulin, a bi-functional modulator of inflammation and coagulation in sepsis (2011)
  • Author(s): Okamoto, T., Tanigami, H., Suzuki, K., Shimaoka, M.
  • Journal Title: Critical Care Research and Practice
  • Peer Reviewed
• [Journal Article] Connexin32 protects against vascular inflammation by modulating inflammatory cytokine expression by endothelial cells (2011)
  • 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
  • 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DIC (2011)
  • Author(s): 岡本貴行、鈴木宏治
  • Journal Title: Thrombosis Medcine Volume: 11月号
• [Journal Article] An in vitro method for screening anti-platelet agents using a microchannel array flow analyzer (2010)
  • Author(s): Kamada, H., Okamoto, T., Hayashi, T., Suzuki, K.
  • Journal Title: Biorheology Volume: 47 Pages: 153-161
  • Peer Reviewed
• [Journal Article] Activated protein C stimulates osteoblast proliferation via endothelial protein C receptor (2010)
  • 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
  • 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
• [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
• [Presentation] Connexin32 regulates pro-coagulant activity of endothelial cells due to modulating tissue factor expression during inflammation (2011)
  • Author(s): Takayuki Okamoto, Tatsuya Hayashi, Koji Suzuki
  • Organizer: 2011 International Gap Junction Conference
  • Place of Presentation: ゲント大学
  • Year and Date: 20110806-11
• [Presentation] Gap junction protein, connexin32 regulates expression of tissue factor and inflammatory cytokines in the endothelial cells (2011)
  • 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
  • Year and Date: 20110723-28
• [Presentation] Effect of protein C inhibitor on lipopolysaccharide-induced vascular permeability (2011)
  • 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
  • Year and Date: 20110723-28
• [Presentation] Anticoagulant activated protein C suppresses osteoclast differentiation via endothelial protein C receptor (2011)
  • 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
  • Year and Date: 20110723-28
• [Presentation] Effect of endotoxin and inflammatory cytokines on protein S and C4B-binding expressions in the liver HepG2 cells (2011)
  • 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
  • Year and Date: 20110723-28
• [Presentation] The inhibition of lung metastasis by inactivation of coagulation activity may lead to dissemination of tumor cells (2011)
  • 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
  • Year and Date: 20110723-28
• [Presentation] Protein C inhibitor inhibits tumor cell growth, but promotes tumor cell metastasis by its procoagulant properties in vivo (2011)
  • 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
  • Year and Date: 20110723-28
• [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
  • Year and Date: 20101209-10
• [Presentation] Connexin32, a gap junction protein, modulates inflammatory cytokine expression in vascular endothelial cells (2010)
  • 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
  • Year and Date: 20101013-16
• [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