The novel molecular mechanism of membrane type1 matrix metallo proteinase(MT1-MMP) in vascular inflammation

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790718
• 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 福島県立医科大学, 医学部, 助教 (30404867)
• Project Period (FY): 2010 – 2011
• Keywords: HMGB-1 / RAGE / マトリックスメタロプロテアーゼ / 動脈硬化 / シグナル伝達 / 血管炎症

Research Abstract

HMGB-1, which is an important mediator in vascular inflammation, causes the phosphorylation of NF-kB and activation of RhoA/Rac1 through AGE receptors in endothelial cells. Tissue factor is upregulated via these signaling pathways. We provide the evidence that MT1-MMP modulates these signal transductions. We also mentioned for the first time to regulation of the expression of endothelial NO synthase by HMGB-1. These results will be reported in the European Society of Cardiology in 2012.

Research Products

• [Journal Article] Adaptive servo ventilation improves cardiac dysfunction and prognosis in chronic heart failure patients with Cheyne-Stokes respiration (2011)
  • Author(s): Yoshihisa A, Shimizu T, Owada T, Nakamura Y, Iwaya S, Yamauchi H, Miyata M, Hoshino Y, Sato T, Suzuki S, Sugimoto K, Yamaki T, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Journal Title: Int Heart J Volume: 52 Pages: 218-223
  • Peer Reviewed
• [Journal Article] Crucial role of membrane type 1 matrix metalloproteinase(MT1-MMP) in RhoA/Rac1-dependent signaling pathways in thrombin-stimulated endothelial cells (2011)
  • Author(s): Ando K, Ishibashi T, Ohkawara H, Inoue N, Sugimoto K, Uekita H, Hu C, Okamoto Y, Takuwa Y, Takeishi Y.
  • Journal Title: J Atheroscler Thromb Volume: 18 Pages: 762-773
  • Peer Reviewed
• [Journal Article] Involvement of membrane type 1-matrix metalloproteinase(MT1-MMP) in RAGE activation signaling pathways (2011)
  • Author(s): Kamioka M, Ishibashi T, Ohkawara H, Nagai R, Sugimoto K, Uekita H, Matsui T, Yamagishi S, Ando K, Sakamoto T, Takuwa Y, Wada I, Shiomi M, Maruyama Y, Takeishi Y.
  • Journal Title: J Cell Physiol Volume: 226 Pages: 1554-1563
  • Peer Reviewed
• [Journal Article] Advanced glycation end product-mediated matrix metallo-proteinase-9 and apoptosis via renin-angiotensin system in type 2 diabetes (2010)
  • Author(s): Ishibashi T, Kawaguchi M, Sugimoto K, Uekita H, Sakamoto N, Yokoyama K, Maruyama Y, Takeishi Y.
  • Journal Title: J Atheroscler Thromb Volume: 17 Pages: 578-589
  • Peer Reviewed
• [Journal Article] Blockade of renin-angiotensin system attenuates advanced glycation end products-mediated signaling pathways (2010)
  • Author(s): Kamioka M, Ishibashi T, Sugimoto K, Uekita H, Nagai R, Sakamoto N, Ando K, Ohkawara H, Teramoto T, Maruyama Y, Takeishi Y.
  • Journal Title: J Atheroscler Thromb Volume: 17 Pages: 590-600
  • Peer Reviewed
• [Journal Article] Flow-mediated dilatation identifies impaired endothelial function in patients with sleep apnea syndrome (2010)
  • Author(s): Yoshihisa A, Owada T, Hoshino Y, Miyata M, Misaka T, Sato T, Suzuki S, Sakamoto N, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Ishibashi T, Takeishi Y.
  • Journal Title: Fukushima J Med Sci Volume: 56 Pages: 115-120
  • Peer Reviewed
• [Journal Article] Preventive effect of chronic endothelin type A receptor antagonist on coronary microvascular spasm induced by repeated epicardial coronary artery endothelial denudation in pigs (2010)
  • Author(s): Osugi T, Saitoh S, Matsumoto K, Muto M, Aikawa K, Ohkawara H, Sugimoto K, Kamioka M, Ishibashi T, Maruyama Y.
  • Journal Title: J Atheroscler Thromb Volume: 17 Pages: 54-63
  • Peer Reviewed
• [Journal Article] Preventive effects of pravastatin on thrombin-triggered vascular responses via Akt/eNOS and RhoA/Rac1 pathways in vivo (2010)
  • Author(s): Ohkawara H, Ishibashi T, Saitoh S, Inoue N, Sugimoto K, Kamioka M, Uekita H, Kaneshiro T, Ando K, Takuwa Y, Maruyama Y, Takeishi Y.
  • Journal Title: Cardiovasc Res Volume: 88 Pages: 492-501
  • 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: Cardiovasc Res Volume: 84 Pages: 127-136
  • Peer Reviewed
• [Journal Article] RhoA and Rac1 changes in the atherosclerotic lesions of WHHLMI rabbits (2009)
  • Author(s): Ohkawara H, Ishibashi T, Shiomi M, Sugimoto K, Uekita H, Kamioka M, Takuwa Y, Teramoto T, Maruyama Y, Takeishi Y.
  • Journal Title: J Atheroscler Thromb Volume: 16 Pages: 846-856
  • Peer Reviewed
• [Journal Article] Role of LOX-1 in monocyte adhesion-triggered redox, Akt/eNOS and Ca^<2+> signaling pathways in endothelial cells (2009)
  • Author(s): Sakamoto N, Ishibashi T, Sugimoto K, Sawamura T, Sakamoto T, Inoue N, Saitoh S, Kamioka M, Uekita H, Ohkawara H, Suzuki K, Teramoto T, Maruyama Y, Takeishi Y.
  • Journal Title: J Cell Physiol Volume: 220 Pages: 706-715
  • Peer Reviewed
• [Presentation] Adaptive servo ventilation improves cardiac function and prognosis in chronic heart failure patients with Cheyne-Stokes respiration after cardiac resynchronization therapy (2011)
  • Author(s): Miyata M, Yoshihisa A, Suzuki S, Yamada S, Kamioka M, Kamiyama Y, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Orlando, Florida USA
  • Year and Date: 20111112-1116
• [Presentation] Overnight use of adaptive servo ventilation reduces cardiac overload and improves renal function in patients with chronic heart failure and Cheyne-Stokes respiration (2011)
  • Author(s): Yoshihisa A, Suzuki S, Miyata M, Sato T, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitho S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Orlando, Florida USA
  • Year and Date: 20111112-1116
• [Presentation] Adaptive servo ventilation improves cardiac function and long term prognosis in heart failure patients with Cheyne-Stokes respiration (2011)
  • Author(s): Yoshihisa A, Miyata M, Sato T, Suzuki S, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Congress of the European Society of Cardiology
  • Place of Presentation: Paris, France
  • Year and Date: 20110827-0831
• [Presentation] Non-invasive detection of vascular dysfunction in sleep apnea syndrome by cardio-ankle vascular index and flow-mediated dilatation (2011)
  • Author(s): Yoshihisa A, Miyata M, Sato T, Suzuki S, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Congress of the European Society of Cardiology
  • Place of Presentation: Paris, France
  • Year and Date: 20110827-0831
• [Presentation] Tenascin-C level is related to coronary plaque rupture in patients with acute coronary syndrome (2011)
  • Author(s): Sakamoto N, Nakazato K, Mizukami H, Suzuki S, Sugimoto K, Yamaki T, Kunii H, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Congress of the European Society of Cardiology
  • Place of Presentation: Paris, France
  • Year and Date: 20110827-0831
• [Presentation] Acute benefical impact of adaptive servo ventilation on hemodynamic data in heart failure patients with Cheyne-Stokes respiration (2011)
  • Author(s): Miyata M, Yoshihisa A, Sato T, Suzuki S, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Congress of the European Society of Cardiology
  • Place of Presentation: Paris, France
  • Year and Date: 20110827-0831
• [Presentation] Adaptive servo ventilation improves cardiac function and prognosis in heart failure patients with Cheyne-Stokes respiration (2010)
  • Author(s): Yoshihisa A, Sato T, Suzuki S, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 20101113-1117
• [Presentation] MT1-MMP controls Akt-dependent Fox01 activation in TNF-α-induced signaling pathways of endothelial cell apoptosis and haemostasis (2010)
  • Author(s): Ohkawara H, Ishibashi T, Ando K, Sugimoto K, Sakamoto N, Uekita H, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 20101113-1117
• [Presentation] MT1-MMP forms a complex with Gi and regulates eNOS expression at posttranscriptional mechanism in oxidized LDL stimulated-endothelial cells (2010)
  • Author(s): Sugimoto K, Ishibashi T, Ohkawara H, Uekita H, Takuwa Y, Kurabayashi M, Teramoto T, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 20101113-1117
• [Presentation] Soluble lectin-like oxidized LDL receptor-1(LOX-1) and LOX index are useful biomarkers for vulnerable plaques (2010)
  • Author(s): Misaka T, Kunii H, Nakazato K, Mizukami H, Sakamoto N, Sugimoto K, Saitoh S, Sawamura T, Uchida K, Ishibashi T, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 20101113-1117
• [Presentation] Membrane Type I Matrix Metalloproteinase(MT1-MMP) mediates thrombin-induced RhoA/Rac1 activation and their downstream signaling in endothelial cells (2010)
  • Author(s): Ando K, Ishibashi T, Ohkawara H, Sugimoto K, Sakamoto N, Okamoto Y, Takuwa Y, Takeishi Y.
  • Organizer: Congress of the European Society of Cardiology
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 20100828-0901
• [Presentation] LOX-1 cooperates with renin-angiotensin system in monocyte adhesion-induced redox-sensitive and Ca^<2+> signaling pathways in endothelial cells (2010)
  • Author(s): Sakamoto N, Ishibashi T, Sugimoto K, Ohkawara H, Inoue N, Sawamura T, Takeishi Y.
  • Organizer: Congress of the European Society of Cardiology
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 20100828-0901
• [Presentation] Pivotal role of receptor for advanced glycation end products(RAGE) in hyperlipidemia-dependent atherosclerosis and molecular regulation (2010)
  • Author(s): Uekita H, Ishibashi T, Shiomi M, Sugimoto K, Ohkawara H, Kamioka M, Yamagishi S, Teramoto T, Koyama H, Ohtsuka S, Itabe H, Takeishi Y.
  • Organizer: 20th World Congress of the International Society for Heart Research(ISHR)
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20100513-0516
• [Presentation] LOX-1 cooperates with renin-angiotensin system(RAS) in monocyte adhesion-induced redox-sensitive and Ca^<2+> signaling pathways in endothelial cells(ECs) (2010)
  • Author(s): Sakamoto N, Ishibashi T, Sugimoto K, Ohkawara H, Sakamoto T, Inoue N, Sawamura T, Takeishi Y.
  • Organizer: 20th World Congress of the International Society for Heart Research(ISHR)
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20100513-0516
• [Presentation] Elevated soluble lectin-like oxidized LDL receptor-1(LOX-1) in coronary circulation of patients with acute coronary syndrome (2010)
  • Author(s): Kunii H, Hoshino Y, Misaka T, Mizukami H, Sakamoto N, Sugimoto K, Nakazato K, Fujita Y, Sawamura T, Ishibashi T, Takeishi Y.
  • Organizer: American College of Cardiology, 59th Annual Scientific Session
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20100314-0316
• [Presentation] High circulating levels of tenascin-c were associated with coronary arterial calcification in patients with stable effort angina pectoris (2010)
  • Author(s): Sakamoto N, Nakazato K, Kunii H, Misaka T, Mizukami H, Sugimoto K, Saitoh S, Ishibashi T, Takeishi Y.
  • Organizer: American College of Cardiology, 59th Annual Scientific Session
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20100314-0316
• [Presentation] LOX-1 mediates renin-angiotensin system(RAS)-dependent redox-sensitive and Ca^<2+> signaling pathways induced in endothelial cells by monocyte adhesion (2009)
  • Author(s): Sakamoto N, Ishibashi T, Sugimoto K, Sakamoto T, Ohkawara H, Sawamura T, Inoue N, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 20091114-1118
• [Presentation] Akt cooperates with membrane type 1-matrix metalloproteinase(MT1-MMP) in TNF-α-induced signaling pathways of endothelial dysfunction and haemostasis (2009)
  • Author(s): Ohkawara H, Ishibashi T, Ando K, Sugimoto K, Uekita H, Sakamoto N, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 20091114-1118
• [Presentation] Cooperation of MT1-MMP and LOX-1 for RhoA-and Rac1-dependent signaling pathways in oxidized LDL-mediated endothelial dysfunction and atherosclerosis (2009)
  • Author(s): Sugimoto K, Ishibashi T, Sawamura T, Uekita H, Kamioka M, Inoue N, Shiomi M, Takuwa Y, Teramoto T, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association
  • Place of Presentation: Orlando, Florida, USA
  • Year and Date: 20091114-1118
• [Presentation] Membrane type matrix metalloproteinase-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: Congress of the European Society of Cardiology
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20090829-0902
• [Presentation] Crucial role of LOX-1 in monocyte adhesion-triggered NADPH oxidase-dependent, Akt/eNOS and Ca^<2+> signaling pathways in endothelial cells (2009)
  • Author(s): Sakamoto N, Ishibashi T, Sugimoto K, Sawamura T, Sakamoto T, Ohkawara H, Saitoh S, Inoue N, Teramoto T, Takeishi Y.
  • Organizer: Congress of the European Society of Cardiology
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20090829-0902
• [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-Molecular Mechanisms of Cardiovascular Disease
  • Place of Presentation: Lake Las Vegas, Nevada, USA
  • Year and Date: 20090720-0723
• [Presentation] Integral role of receptor for advanced glycation end products(RAGE) in nondiabetic atherosclerosis (2009)
  • Author(s): Uekita H, Ishibashi T, Sugimoto K, Shiomi M, Yamagishi S, Koyama H, Takeishi Y.
  • Organizer: Basic Cardiovascular Sciences Conference 2009-Molecular Mechanisms of Cardiovascular Disease
  • Place of Presentation: Lake Las Vegas, Nevada, USA
  • Year and Date: 20090720-0723