2019/07/18 by Charlotte Thålin, Yohei Hisada, Staffan Lundström +2 · 1 citation
Immunology and Microbiology · Medicine · Biochemistry, Genetics and Molecular Biology · #Neutrophil, Myeloperoxidase and Oxidative Mechanisms #Vasculitis and related conditions #Inflammasome and immune disorders #Neutrophil extracellular traps #Tissue factor pathway inhibitor #Tissue factor #Von Willebrand factor #Thrombus #Platelet #Hemostasis #Thrombosis #Cell biology #Coagulation #Biology #Extracellular #Immunology #Medicine #Cancer research #Inflammation #Internal medicine
paper · doi:10.1161/atvbaha.119.312463
openalex publication_date 2019/07/18 · openalex created_date 2019/07/30 · openalex updated_date 2026/07/31
Recent studies have demonstrated a role of neutrophils in both venous and arterial thrombosis. A key prothrombotic feature of neutrophils is their ability to release web-like structures composed of DNA filaments coated with histones and granule proteins referred to as neutrophil extracellular traps (NETs). NETs were discovered over a decade ago as part of our first line of host defense against invading microorganisms. Although NETs have a protective role against pathogens, recent data suggest that an uncontrolled and excessive NET formation within the vasculature may contribute to pathological thrombotic disorders. In vitro studies suggest that NETs promote vessel occlusion by providing a scaffold for platelets, red blood cells, extracellular vesicles, and procoagulant molecules, such as von Willebrand factor and tissue factor. In addition, NET components enhance coagulation by both activating the intrinsic pathway and degrading an inhibitor of the extrinsic pathway (tissue factor pathway inhibitor). NET formation has, therefore, been proposed to contribute to thrombus formation and propagation in arterial, venous, and cancer-associated thrombosis. This review will describe animal and human studies suggesting a role of NETs in the pathogenesis of various thrombotic disorders. Targeting NETs may be a novel approach to reduce thrombosis without affecting hemostasis.