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Semin Thromb Hemost 2018; 44(02): 151-158
DOI: 10.1055/s-0037-1607431
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Factor VII-Activating Protease: Hemostatic Protein or Immune Regulator?

Sacha Zeerleder
1   Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands
2   Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
› Author Affiliations
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Publication History

Publication Date:
24 November 2017 (online)

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Abstract

Factor VII (FVII)-activating protease (FSAP) is a serine protease in plasma, which was initially described to play a role in coagulation by activation of FVII, independent of tissue factor, and in fibrinolysis by cleavage of single-chain urokinase. Recent studies, however, suggest that FSAP-mediated FVII cleavage is negligible and that FSAP may exert procoagulant functions via cleavage of tissue factor pathway inhibitor. Meanwhile, many substrates of FSAP have been identified, such as platelet-derived growth factor, basic fibroblast growth factor/epidermal growth factor, histones, and high-molecular-weight kininogen. FSAP has also shown to induce DNA released from dead cells. Given its propensity for autoproteolysis and degradation, studies on the activation and regulation of FSAP are difficult to perform. Recent animal studies suggest a role of FSAP in the pathogenesis of arteriosclerosis, vascular integrity and probably also in the regulation of coagulation initiation. This review will focus on the biochemical properties of FSAP, regulation of FSAP activation, and finally its role in vascular disease and acute systemic inflammatory diseases, such as sepsis.

Keywords

factor VII-activating protease - inflammation - hyaluronic acid binding protein 2 - nucleosomes - C1-inhibitor - PAI-1 - tissue factor pathway inhibitor
 

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