Role of LOX-1-MT1-MMP axis in oxidized LDL-triggered endothelial dysfunction

• Project/Area Number: 20790538
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Fukushima Medical University
• Principal Investigator: SUGIMOTO Koichi Fukushima Medical University, 医学部, 助教 (30404867)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 分子血管病態学 / シグナル伝達 / 動脈硬化 / 血管内皮機能不全 / 酸化LDL受容体 / マトリックスメタロプロテアーゼ

Research Abstract

We provided a new evidence that LOX-1, which is a receptor for oxidized LDL, forms a complex with MT1-MMP and regulates RhoA and Rac1 activation as well as eNOS and NADPH oxidase activation and ROS generation induced by oxidized LDL in endothelial cells. These results were published in Cardiovascular Research.

Research Products

• [Journal Article] LOX-1-MT1-MMP axis is crucial for RhoA and Rac1 activation induced by oxidized low-density lipoprotein in endothelial cells. (2009)
  • Author(s): Sugimoto K, Ishibashi T, Sawamura T, Inoue N, Kamioka M, Uekita H, Ohkawara H, Sakamoto T, Sakamoto N, Okamoto Y, Takuwa Y, Kakino A, Fujita Y, Tanaka T, Teramoto T, Maruyama Y, Takeishi Y.
  • Journal Title: Cardiovasc Res. 84(1) Pages: 127-136
  • Peer Reviewed
• [Journal Article] LOX-1-MT1-MMP Axis is Crucial for RhoA and Rac1 Activation Induced by Oxidized Low-Density Lipoprotein in Endothelial Cells. (2009)
  • Author(s): Sugimoto K, Ishibashi T, Sawamura T, Inoue N, Kamioka M, Uekita H, Ohkawara H, Sakamoto T, Sakamoto N, Okamoto Y, Takuwa Y, Kakino A, Fujita Y, Tanaka T, Teramoto T, Maruyama Y, Takeishi Y.
  • Journal Title: Cardiovascular Research 84 Pages: 127-136
  • Peer Reviewed
• [Presentation] MT1-MMP forms a complex with L OX-1 and plays a crucial role in oxi dized LDL-induced endothelial dysfun ction via RhoA/Rac1 activation. (2010)
  • Author(s): K. Sugimoto, T. Ishibashi, T. Sawamura, H. Uekita, H. Ohkawara, N. Inoue, Y. Takuwa, M. Shiomi, T. Teramoto, Y. Takeishi.
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-07
• [Presentation] MT1-MMP forms a complex with LOX-1 and plays a crucial role in oxidized LDL-induced endothelial dysfunction via RhoA/Rac1 activation (2010)
  • Author(s): K.Sugimoto, T.Ishibashi, T.Sawamura, H.Uekita, H.Ohkawara, N.Inoue, Y.Takuwa, M.Shiomi, T.Teramoto, Y.Takeishi
  • Organizer: 第74回 日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-03-07
• [Presentation] RhoA・Rac1活性化を介する酸化LD Lによる血管内皮細胞機能不全の新しい分子機序:MT1-MMPの関与 (2010)
  • Author(s): 杉本浩一、石橋敏幸、沢村達也、上北洋徳、上岡正志、井上信孝、坂本信雄、大河原浩、多久和陽、寺本民夫、塩見雅志、竹石恭知
  • Organizer: 日本心脈管作動物質学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-02-05
• [Presentation] RhoA-Rac1活性化を介する酸化LDLによる血管内皮細胞機能不全の新しい分子機序:MT1-MMPの関与 (2010)
  • Author(s): 杉本浩一、石橋敏幸、沢村逹也、上北洋徳、上岡正志、井上信孝、坂本信雄、大河原浩、多久和陽、寺本民夫、塩見雅志、竹石恭知
  • Organizer: 日本心脈管作動物質学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-02-05
• [Presentation] 酸化LDLによる血管内皮機能不全におけるLOX-1/MT1-MMP系の役割 (2009)
  • Author(s): 杉本浩一、石橋敏幸、竹石恭知
  • Organizer: 第1回Advance研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-12-26
• [Presentation] 酸化LDLによる血管内皮と機能不全におけるLOX-1/MT1-MMP系の役割 (2009)
  • Author(s): 杉本浩一、石橋敏幸、竹石恭知
  • Organizer: 第1回 Advance研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-12-26
• [Presentation] Cooperation of MT1-MMP and LOX-1 for RhoAand Rac1-dependent signaling pathways in oxidized LDL-mediated endothelial dysfunction. (2009)
  • Author(s): K. Sugimoto, T. Ishibashi, T. Sawamura, H. Uekita, M. Kamioka, N. Inoue, M. Shiomi, Y. Takuwa, T. Teramoto, Y. Takeishi.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: オーランド
  • Year and Date: 2009-11-14
• [Presentation] Cooperation of MT1-MMP and LOX-1 for RhoA- and Rac1-dependent signaling pathways in oxidized LDL-mediated endothelial dysfunction (2009)
  • Author(s): K.sugimoto, T.Ishibashi, T.Sawamura, H.Uekita, M.Kamioka, N.Inoue, M.Shiomi, Y.Takuwa, T.Teramoto, Y.Takeishi
  • Organizer: Scientific Sessions of American Heart Association 2009
  • Place of Presentation: オーランド(アメリカ合衆国)
  • Year and Date: 2009-11-14
• [Presentation] Membrane type matrix metalloprotainase-1 (MT1-MMP) is a cell surface modifier of RhoA/Rac1 -mediated signaling pathways and forms a complex with LOX-1 in oxidized LDL-induced endothelial dysfunction. (2009)
  • Author(s): Sugimoto K, Ishibashi T, Sawamura T, Kamioka M, Uekita H, Ohkawara H, Inoue N, Takuwa Y, Teramoto T, Takeishi Y.
  • Organizer: Europian Society of Carciology Cogress 2009
  • Place of Presentation: バルセロナ
  • Year and Date: 2009-08-29
• [Presentation] Membrane type matrix metalloprotainase-1 (MT1-MMP) is a cell surface modifier of RhoA/Rac1-mediated signaling pathways and forms a complex with LOX-1 in oxidized LDL-induced endothelial dysfunction. (2009)
  • Author(s): K.Sugimoto, T.Ishibashi, T.Sawamura, M.Kamioka, H.Uekita, H.Ohkawara, N.Inoue, Y.Takuwa, T.Teramoto, Y.Takeishi
  • Organizer: Congress of the European Society of Cardiology 2009
  • Place of Presentation: バルセロナ(スペイン)
  • Year and Date: 2009-08-29
• [Presentation] New insights of LOX-1-MT1-MMP Axis into RhoA and Rac1 Activation Induced by Oxidized Low-Density Lipoprotein in Endothelial Cells. (2009)
  • Author(s): Sugimoto K, Ishibashi T, Sawamura T, Uekita H, Takuwa Y, Teramoto T, Shiomi M, Takeishi Y.
  • Organizer: Basic Cardiovascular Sciences Conference 2009
  • Place of Presentation: ヘンダーソン
  • Year and Date: 2009-07-20
• [Presentation] New insights of LOX-1-MT1-MMP Axis into RhoA and Rac1 Activation Induced by Oxidized Low-Density Lipoprotein in Endothelial Cells (2009)
  • Author(s): K.Sugimoto, T.Ishibashi, T.Sawamura, H.Uekita, Y.Takuwa, T.Teramoto, M.Shiomi, Y.Takeishi
  • Organizer: Basic Cardiovascular Sciences Conference 2009, American Heart Association
  • Place of Presentation: ヘンダーソン(アメリカ合衆国)
  • Year and Date: 2009-07-20
• [Presentation] Silencing of MT1-MMP Blocks Ox-LDL-Induced Rac1/NADPH Oxidas e Activity and Reactive Oxygen Specie s (ROS) Generation. (2009)
  • Author(s): K. Sugimoto, T. Ishibashi, N. Inoue, Y. Takuwa, T. Teramoto, Y. Takeishi.
  • Organizer: 第41回日本動脈硬化学会学術総会
  • Place of Presentation: 下関
  • Year and Date: 2009-07-17
• [Presentation] Silencing of MT1-MMP Blocks Ox-LDL-Induced Rac1/NADPH Oxidase activity and Reactive Oxygen Species (ROS) Generation (2009)
  • Author(s): K.Sugimoto, T.Ishibashi, N.Inoue, Y.Takuwa, T.Teramoto, Y.Takeishi
  • Organizer: 第41回 日本動脈硬化学会学術総会
  • Place of Presentation: 下関
  • Year and Date: 2009-07-17
• [Presentation] LOX-1-MT1-MMP Axis in RhoA and Racl activation through Gi induced by oxidizes low-density lipoprotein in endothelial cells (2008)
  • Author(s): 杉本浩一
  • Organizer: 第16回日本血管生物医学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2008-12-03
• [Presentation] Lox-1-MT1-MMP系は酸化LDL刺激血管内皮細胞においてGiを介するRhoA, Raclの活性化に重要である (2008)
  • Author(s): 杉本浩一
  • Organizer: 第40回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 筑波
  • Year and Date: 2008-07-10