Figure 1 Mechanisms of blood coagulation and its regulation pathways. AT, antithrombin; HCII, heparin cofactor II; TFPI, tissue factor pathway inhibit
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1 Online publication October 3, 2011 総 説 特集 : 血栓止血, 凝固線溶 (1) 血栓形成機構 : 最近の知見 血液凝固機序 血栓形成と細胞機能に及ぼす凝固因子の作用機序 要 旨 : J Jpn Coll Angiol, 2011, 51: Key words: atrial fibrillation, deep venous thrombosis, thrombotic embolism, blood coagulation, anticoagulation systems はじめに 血栓症の発症機序 血液凝固機序 1 tissue factor; TF VIIa TF Protein disulfide isomerase PDI de-encryption TF XII XI TF XI THE JOURNAL of JAPANESE COLLEGE of ANGIOLOGY Vol. 51 No
2 Figure 1 Mechanisms of blood coagulation and its regulation pathways. AT, antithrombin; HCII, heparin cofactor II; TFPI, tissue factor pathway inhibitor; ZPI, protein Z-dependent protease inhibitor; APC, activated protein C; PCI, protein C inhibitor; C4BP, C4b-binding protein; TM, thrombomodulin; EPCR, endothelial protein C receptor; PL, phospholipid Fig. 1 MP MP TF MP P-selectin PSGL-1 CD15 TF MP P-selectin MP TF 1 2 TF K γ-carboxyglutamic acid Gla VII IX X Va VIIIa VIIa IXa Xa X Fig. 2 IXa X VIIIa 10 Xa Va 30 VIIIa Figure 2 Amplification of blood coagulation on platelets (Modified from Mackman N, et al. ATVB 27: 1687, 2007). IXa X Va Xa MP MP 288 脈管学 Vol. 51 No. 3
3 Table 1 Protease inhibitors on blood coagulation factors Inhibitors MW Concentration (μg/ml) Target proteases Antithrombin (AT) 58, thrombin, Xa, IXa Heparin cofactor (HCII) 66, Thrombin α1antitrypsin (α1at) 52, XIa, APC C1inhibitor (C1INH) 104, Plasma kallikrein, XIIa Protein C inhibitor (PCI) 57,000 4 APC, plasma kallikrein Tissue factor pathway inhibitor (TFPI) 38, (ng/ml) VIIa TF, Xa Protein Z-dependent protease inhibitor (ZPI) 72, Xa, XIa P-selectin XIII XIIIa XIIIa 血液凝固制御機序 C Fig. 1 1 tissue factor pathway inhibitor; TFPI AT II HCII heparan sulfate proteoglycan; HSPG Table 1 Z ZPI 1 TFPI TFPI HSPG VIIa Xa TFPI TFPI HSPG 2 AT AT ATIII Xa AT HSPG AT AT AT AT AT AT AT AT 3 HCII HCII HCII HSPG HCII HCII 4 ZPI Z PZ K 1998 PZ September 25,
4 Xa PZ ZPI ZPI Xa PZ Ca 2+ IXa PZ ZPI ZPI 2 C PC PC PC thrombomodulin; TM PC endothelial protein C receptor; EPCR PC PC activated protein C; APC Va VIIIa PC Fig. 1 APC S PS EPCR APC PC APC APC protein C inhibitor; PCI PC 1 C PC PC K PC EPCR EPCR PC TM APC PS PS Va VIIIa PC EPCR APC Protease-activated receptor-1; PAR-1 NF-κB APC PAR-1 Figure 3 Protective signaling pathways of activated protein C in endothelial cells. 1 Sphingosine-1-phosphate; S1P S1P S1P S1P 3 Fig. 3 PAR-1 EPCR APC PAR-1 PAR-1 Gq G12/13 RhoA NF-κB TF APC PC EPCR EPCR PAR-1 Caveolin EPCR APC PAR-1 Gi Rac1 4 APC β1/β3 5 CD11b/CD18 EPCR 6 EPCR CD PC PC DIC 290 脈管学 Vol. 51 No. 3
5 2 TM TM V VIII PC TM Thrombin-activated fibrinolysis inhibitor; TAFI TAFIa t-pa TAFI TM High mobility group box-1; HMGB-1 TM HMGB-1 9 HMGB-1 p53 NF-κB DNA TM HMGB-1 PC TM TM DIC DIC TM TM 3 S PS PS K APC PS APC Va VIIIa APC Va VIIIa PS C4b C4BP PS APC PS TFPI PS PS PS C4BP PS PS PS EGF SNP 4 EPCR EPCR PC APC TM PC PAR-1 APC EPCR EPCR TM 5 C PCI PCI TM APC PC PCI TM TAFI PCI HSPG PCI PCI PCI PCI PCI PC PCI 10 おわりに September 25,
6 C APC APC 文献 1 Rauch U, Bonderman D, Bohrmann B, et al: Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood 2000; 96: Mackman N, Tilley RE, Key NS: Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol 2007; 27: Riewald M, Schuepbach RA: Protective signaling pathways of activated protein C in endothelial cells. Arterioscler Thromb Vasc Biol 2008; 28: Bae JS, Rezaie AR: Protease activated receptor 1 (PAR-1) activation by thrombin is protective in human pulmonary artery endothelial cells if endothelial protein C receptor is occupied by its natural ligand. Thromb Haemost 2008; 100: Elphick GF, Sarangi PP, Hyun YM, et al: Recombinant human activated protein C inhibits integrin-mediated neutrophil migration. Blood 2009; 113: Cao C, Gao Y, Li Y, et al: The efficacy of activated protein C in murine endotoxemia is dependent on integrin CD11b. J Clin Invest 2010; 120: Kerschen E, Hernandez I, Zogg M, et al: Activated protein C targets CD8+ dendritic cells to reduce the mortality of endotoxemia in mice. J Clin Invest 2010; 120: Xu J, Zhang X, Pelayo R, et al: Extracellular histones are major mediators of death in sepsis. Nature Med 2009; 15: Abeyama K, Stern DM, Ito Y, et al: The N-terminal domain of thrombomodulin sequesters high-mobility group-b1 protein, a novel antiinflammatory mechanism. J Clin Invest 2005; 115: Suzuki K: The multi-functional serpin, protein C inhibitor: beyond thrombosis and hemostasis. J Thromb Haemost 2008; 6: Mechanisms of Blood Coagulation Factors on Thrombus Formation and Cell Activation in Thrombosis and Hemostasis Koji Suzuki Suzuka University of Medical Sciences, Faculty of Pharmaceutical Science, Mie, Japan Key words: atrial fibrillation, deep venous thrombosis, thrombotic embolism, blood coagulation, anticoagulation systems Activation of the blood coagulation system is initiated by the binding of factor VIIa to tissue factor, which is deencrypted on injured endothelial cells and many other extravascular cells. Thrombin, an important coagulation protease, is a multifunctional protein that, besides its functions in hemostasis and thrombosis (atrial fibrillation, deep venous thrombosis, and thrombotic embolism), has many cellular effects that link the coagulation system with the inflammatory response, such as wound healing, atherosclerosis, angiogenesis, tumor cell growth, and metastasis. On the other hand, several anticoagulation systems play roles related to the vascular endothelial cells: the tissue factor pathway inhibitor system, antithrombin system, and protein C anticoagulant system. Congenital deficiencies of factors in the anticoagulant systems cause severe thrombotic diseases. The protein C anticoagulant system is the most important for maintaining blood fluidity in the vessels. Thrombin activates protease-activated receptor-1 (PAR-1) on the cells, which induces inflammation in the cells. Activated protein C (APC) also activates PAR-1 in the presence of endothelial protein C receptor (EPCR), which induces anti-inflammation in the cells. The PAR-1 activations by thrombin and APC/EPCR may play important roles in the expression of specific cellular responses in several physiological processes and in the pathogenesis of several diseases. (J Jpn Coll Angiol, 2011, 51: ) 292 Online publication October 3, 2011 脈管学 Vol. 51 No. 3
2 はじめに 血栓症とは 140 2/3 4 DIC: disseminated intravascular coagulation 3 Virchow's triad : R. K. Virchow 表 1 各種静脈血栓症の発症要因 C S C Factor V Leiden*
1 総 説 血栓症治療薬の進歩 - 新しい経口抗凝固薬を中心に - 鈴木 宏治 キーワード :Xa DIC 要旨 NVAF DVT PE 3 Virchow's triad K Xa NVAF DVT PE 2 はじめに 血栓症とは 140 2/3 4 DIC: disseminated intravascular coagulation 3 Virchow's triad : R. K. Virchow
Table 1 Isolated venous thrombi in soleal muscle by ultrasonography US finding Acute Chronic Total No. Early stage non-retracted slightl
Online publication October 8, 2010 原 著 第 50 回総会座長推薦論文 孤立性ひらめ筋内静脈血栓と抗核抗体との関連 1 2 要旨 : 89 116 D 3 30 70 63 26 100 J Jpn Coll Angiol, 2010, 50: 417 422 Key words: isolated soleal venous thrombi, recurrent
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Online publication October 3, 2011 総 説 特集 : 血栓止血, 凝固線溶 (2) 抗血栓薬の新しい展開 新規抗血小板薬の開発 要旨 : J Jpn Coll Angiol, 2011, 51: Key words: atherothrombosis
Online publication October 3, 2011 総 説 特集 : 血栓止血, 凝固線溶 (2) 抗血栓薬の新しい展開 新規抗血小板薬の開発 要旨 : J Jpn Coll Angiol, 2011, 51: 301 307 Key words: atherothrombosis, P2Y 12, CYP2C19, GPVI, α IIbβ 3 はじめに 3 atherothrombosis
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Online publication October 3, 2011 総 説 特集 : 血栓止血, 凝固線溶 (1) 血栓形成機構 : 最近の知見 血栓形成過程 : オーバービュー 要旨 : J Jpn Coll Angiol, 2011, 51: Key words: thromb
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