血管炎症における新規分子MT1-MMPの関与

2011 年度 研究成果報告書

• 研究課題/領域番号: 22790718
• 研究種目: 若手研究(B)
• 配分区分: 補助金
• 研究分野: 循環器内科学
• 研究機関: 福島県立医科大学
• 研究代表者: 杉本 浩一 福島県立医科大学, 医学部, 助教 (30404867)
• 研究期間 (年度): 2010 – 2011
• キーワード: 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

研究概要

血管炎症において重要なメディエーターであるHMGB-1は血管内皮細胞のAGE受容体を介してRhoA/Rac1の活性化とNF-kBのリン酸化を引き起こし、組織因子の産生を亢進させ、このシグナル伝達の制御にMT1-MMPが重要な役割を果たしていることを本研究で初めて証明した。またHMGB-1による内皮型NO合成酵素の発現調整にも初めて言及し、これらの結果は2012年のヨーロッパ心臓病学会において報告する予定である。

研究成果

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