title: Functional characterization of tissue factor in von Willebrand factor-dependent thrombus formation under whole blood flow conditions.
abstract: Von Willebrand factor (VWF) plays an important role in mediating platelet adhesion and aggregation under high shear rate conditions. Such platelet aggregates are strengthened by fibrin-network formation triggered by tissue factor (TF). However, little is known about the role of TF in VWF-dependent thrombus formation under blood flow conditions. We evaluated TF in thrombus formation on immobilized VWF under whole blood flow conditions in an in vitro perfusion chamber system. Surface-immobilized TF amplified intra-thrombus fibrin generation significantly under both low and high shear flow conditions, while TF in sample blood showed no appreciable effects. Furthermore, immobilized TF enhanced VWF-dependent platelet adhesion and aggregation significantly under high shear rates. Neutrophil cathepsin G and elastase increased significantly intra-thrombus fibrin deposition on immobilized VWF-TF complex, suggesting the involvement of leukocyte inflammatory responses in VWF/TF-dependent mural thrombogenesis under these flow conditions. These results reveal a functional link between VWF and TF under whole blood flow conditions, in which surface-immobilized TF and VWF mutually contribute to mural thrombus formation, which is essential for normal hemostasis. By contrast, TF circulating in blood may be involved in systemic hypercoagulability, as seen in sepsis caused by severe microbial infection, in which neutrophil inflammatory responses may be active.
authors: Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan.
authors: Yasunori
authors: Y
authors: Matsunari
authors: Department of Regulatory Medicine for Thrombosis, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan. sugi-ped@naramed-u.ac.jp.
authors: Mitsuhiko
authors: http://orcid.org/0000-0003-2935-5502
authors: M
authors: Sugimoto
authors: Department of Regulatory Medicine for Thrombosis, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors: Masaaki
authors: M
authors: Doi
authors: Department of Regulatory Medicine for Thrombosis, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors: Hideto
authors: H
authors: Matsui
authors: Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan.
authors: Masahiko
authors: M
authors: Kawaguchi
mesh_terms: D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D056649:Cathepsin G / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000378:metabolism; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D005337:Fibrin; D013925:Thromboplastin; D056649:Cathepsin G
keywords: Blood flow; Fibrin; Thrombus formation; Tissue factor; Von Willebrand factor