title: Tissue factor: A potent stimulator of Von Willebrand factor synthesis by human umbilical vein endothelial cells.
abstract: Inflammation and dysfunction of endothelial cells are thought to be triggers for the secretion of Von Willebrand factor. The aim of this study was to examine the effects of the inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) and the coagulation factors, tissue factor and thrombin on the release and cleavage potential of ultra-large von Willebrand factor (ULVWF) and its cleavage protease by cultured human umbilical vein endothelial cells (HUVEC). HUVEC were treated with IL-6, IL-8, and TNF-α, tissue factor (TF) and thrombin, and combinations thereof for 24 hours under static conditions. The cells were then exposed to shear stress after which the VWF-propeptide levels and the VWF cleavage protease, ADAMTS13 content were measured. All treatments and their combinations, excluding IL-6, significantly stimulated the secretion of VWF from HUVEC. The VWF secretion from the HUVEC was stimulated most by the combination of TF with TNF-α. Slightly lower levels of ADAMTS13 secretion were found with all treatments. This may explain the thrombogenicity of patients with inflammation where extremely high VWF levels and slightly lower ADAMTS13 levels are present.
authors.affiliation: Department of Haematology and Cell Biology, University of the Free State Bloemfontein, South Africa.
authors.forename: Muriel
authors.initials: M
authors.lastname: Meiring
authors.affiliation: Department of Haematology and Cell Biology, University of the Free State Bloemfontein, South Africa.
authors.forename: W
authors.initials: W
authors.lastname: Allers
authors.affiliation: Department of Haematology and Cell Biology, University of the Free State Bloemfontein, South Africa.
authors.forename: E
authors.initials: E
authors.lastname: Le Roux
mesh_terms: D000071120:ADAMTS13 Protein / Q000378:metabolism*; D016207:Cytokines / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D013917:Thrombin / Q000502:physiology; D013925:Thromboplastin / Q000502:physiology*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D016207:Cytokines; D014841:von Willebrand Factor; D013925:Thromboplastin; D013917:Thrombin; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; Endothelium; Inflammation.; Von Willebrand factor