Anti-inflammatory Activity of the Protein Z-Dependent Protease Inhibitor.

The protein Z (PZ)-dependent plasma protease inhibitor (ZPI) is a glycoprotein that inhibits factor XIa and, in the presence of PZ, FXa. Recently, ZPI has been shown to be an acute-phase protein (APP). As usually APPs downregulate the harmful effects of inflammation, we tested whether ZPI could modulate the increase of cytokines observed in inflammatory states.

The Proteolytic Inactivation of Protein Z-Dependent Protease Inhibitor by Neutrophil Elastase Might Promote the Procoagulant Activity of Neutrophil Extracellular Traps in Sepsis.

Septic shock is the archetypal clinical setting in which extensive crosstalk between inflammation and coagulation dysregulates the latter. The main anticoagulant systems are systematically impaired, depleted, and/or downregulated. Protein Z-dependent protease inhibitor (ZPI) is an anticoagulant serpin that not only targets coagulation factors Xa and XIa but also acts as an acute phase reactant whose plasma concentration rises in inflammatory settings.

Serpins in Hemostasis as Therapeutic Targets for Bleeding or Thrombotic Disorders.

Bleeding and thrombotic disorders result from imbalances in coagulation or fibrinolysis, respectively. Inhibitors from the serine protease inhibitor (serpin) family have a key role in regulating these physiological events, and thus stand out as potential therapeutic targets for modulating fibrin clot formation or dismantling. Here, we review the diversity of serpin-targeting strategies in the area of hemostasis, and detail the suggested use of modified serpins and serpin inhibitors (ranging from small-molecule drugs to antibodies) to treat or prevent bleeding or thrombosis.