Protein C Inhibitor Is a Potent Inhibitor of the Thrombin-Thrombomodulin Complex

Abstract

Protein C inhibitor (PCI),

Protein C activation in NIDDM patients

“…On the other hand, the endothelial membranebound TM, besides serving as a co-factor for the thrombin-induced activation of PC, may also exert direct thromboprotective effect by inhibiting the proteolytic and thrombogenic actions of thrombin on other clotting proteins and by accelerating the inhibition of thrombin by plasma serine protease inhibitors such as antithrombin III [9] or PCI [10]. The overall TAR was evaluated by using an in vitro assay, and its values were found to be lower in diabetic patients than in normal control subjects.…”

“…Aside from its role in the thrombin-mediated catalytic activation of PC, TM produces additional anticoagulant effects by inhibiting various thrombin-induced thrombogenic activities such as the proteolysis of fibrinogen, activation of factors Vand XIII, inactivation of PS and inhibition of platelet aggregation [8]. TM also accelerates the inhibition of thrombin by antithrombin III [9] and PCI [10]. These anticoagulant activities of TM are believed to be impaired in diabetic patients as a result of endothelial injury induced proteolytic cleavage of the membrane-bound TM.…”

Protein C inhibitor inhibits breast cancer cell growth, metastasis and angiogenesis independently of its protease inhibitory activity

“…Protein C inhibitor (PCI) was originally identified as a plasma inhibitor of the anticoagulant protease, activated protein C. 1,2 PCI is a member of the serine protease inhibitor (SERPIN) family (SERPINA5); it is also able to inhibit other proteases of the blood coagulation and fibrinolysis system including thrombin, 3 thrombin-thrombomodulin complex, 4 factor Xa, 3 factor XIa, 5 plasma kallikrein 5 and urinary plasminogen activator (uPA). 6 Human plasma PCI is mainly synthesized in the liver, 7 but it is also produced in kidneys and reproductive organs, including testes, seminal vesicles and ovaries.…”

Polimorfismos genéticos relacionados à hemostasia e a sua relação com abortos espontâneos recorrentes

“…A PCa exerce a sua função através da inativação proteolítica dos fatores Va e VIIIa em superfícies que contenham fosfolípides, atenuando a geração de trombina. Esse processo é potencializado pela proteína S, que age como um cofator não enzimático nas reações de inativação (Rezaie et al, 1995;Isermann et al, 2003;Uszyński et al, 2010).…”

“…No processo de coagulação atua: 1-removendo os fibrinopeptídeos A e B da molécula de fibrinogênio para formar os monômeros de fibrina, desta maneira formando o coágulo de fibrina; 2-ativando as plaquetas e 3-promovendo a retroalimentação da ativação de outros fatores da coagulação (fatores XI, VIII e V) (Rezaie et al, 1995;Ariëns et al, 2002). Além desses papéis, a trombina também possui função anticoagulante, uma vez que se liga á trombomodulina na ativação da proteína C (Morser, 2011), e atua na ativação do inibidor da fibrinólise ativado pela trombina (TAFI) (Uszyński et al, 2010).…”