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

2009 Fiscal Year Final Research Report

• 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
• Keywords: 分子血管病態学

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
• [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] 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] 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] 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] 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] 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] 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