活性化プロテインCの抗血栓作用  [in Japanese] Anti-thrombotic effect of activated protein C  [in Japanese]

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Author(s)

    • 勝浦 保宏 KATSUURA Yasuhiro
    • 帝人(株)医薬開発研究所薬理研究部 Pharmacological Research Department, Pharmaceuticals Development Research Laboratories, Teijin Limited

Abstract

活性化プロテインC (Activated Protein C: APC) は血液凝固制御機構を司る重要な生体成分で,分子内のγ-カルボキシグルタミン酸とCa<SUP>2+</SUP>を介し血栓が形成されている細胞膜上に結合し,活性化凝固第V因子や第VIII因子を不活化し凝固カスケードを抑制するため,出血のリスクが少なく強力な抗血栓作用を発揮することが期待される.我々はAPCを成分とする血液分画製剤を血栓症治療薬として開発しているが, APC製剤がヘパリンに比べ出血リスクが少なく抗血栓作用を示すことを汎発性血管内凝固症候群の動物モデルを用いた試験や,臨床試験において実証した.また抗凝固作用とは別に線溶亢進作用を有し,血栓保持を抑制する.さらに白血球活性化を抑制し抗炎症作用を発揮すること,また血管内皮細胞膜に特異的な受容体の存在が発見され,APCの機能との関連が明らかになりつつある. APCは血液凝固線溶系と炎症免疫系の接点に位置し多面的に生体の防御機構を調節していると考えられ,その生理調節能が注目されるとともに, APC製剤の血栓症や炎症疾患への有用性が期待される.

Protein C (PC) is an important anticoagulant protein in blood and converted to its active form, activated protein C (APC), by thrombin bound with thrombomodulin. APC exhibits an anticoagulant effect by the inactivation of FV a and FVIII a. In addition, APC exerts a profibrinolytic effect by inactivation of PAI-1 and inhibition of TAFI activation. APC is strongly anti-thrombotic because of its anticoagulant and profibrinolytic effect. APC has γ-carboxyglutamic acid residues that bind to acidic phospholipids expressed on activated plateles or injured endothelial cells. Thus APC works only at the site where clots are formed and has a weak effect in primary hemostasis; this means that the use of APC is expected not to have any hemorrhagic risk. In both DIC animal models and clinical studies, we confirmed safer amelioration by APC than heparin. Recently, a specific receptor for PC/APC was found on endothelial cell membrane and antiinflammatory effects of APC were also reported. Thus APC is thought to play an important regulatory role in blood coagulation, fibrinolysis and inflammation, especially in thrombotic diseases.

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 116(5), 290-297, 2000-11-01

    The Japanese Pharmacological Society

References:  28

Codes

  • NII Article ID (NAID)
    10008181260
  • NII NACSIS-CAT ID (NCID)
    AN00198335
  • Text Lang
    JPN
  • Article Type
    REV
  • ISSN
    00155691
  • NDL Article ID
    5539850
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z19-247
  • Data Source
    CJP  NDL  J-STAGE 
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