title: Tissue factor is induced by interleukin-33 in human endothelial cells: a new link between coagulation and inflammation.
abstract: Tissue factor (TF) is the primary trigger of coagulation. Elevated levels of TF are found in atherosclerotic plaques, and TF leads to thrombus formation when released upon plaque rupture. Interleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial cells (ECs). Here, we investigated the impact of IL-33 on TF in human ECs, as a possible new link between inflammation and coagulation. IL-33 induced TF mRNA and protein in human umbilical vein ECs and coronary artery ECs. IL-33-induced TF expression was ST2- and NF-κB-dependent, but IL-1-independent. IL-33 also increased cell surface TF activity in ECs and TF activity in ECs-derived microparticles. IL-33-treated ECs reduced coagulation time of whole blood and plasma but not of factor VII-deficient plasma. In human carotid atherosclerotic plaques (n = 57), TF mRNA positively correlated with IL-33 mRNA expression (r = 0.691, p < 0.001). In this tissue, IL-33 and TF protein was detected in ECs and smooth muscle cells by immunofluorescence. Furthermore, IL-33 and TF protein co-localized at the site of clot formation within microvessels in plaques of patients with symptomatic carotid stenosis. Through induction of TF in ECs, IL-33 could enhance their thrombotic capacity and thereby might impact on thrombus formation in the setting of atherosclerosis.
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Austria.|Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stojkovic
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaun
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Austria.
authors.forename: Jose
authors.initials: J
authors.lastname: Basilio
authors.affiliation: Core Facilities, Medical University of Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rauscher
authors.affiliation: Department of Internal Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Austria.
authors.forename: Lena
authors.initials: L
authors.lastname: Hell
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Austria.
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Krychtiuk
authors.affiliation: Ludwig Boltzmann Institute of Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Bonstingl
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: de Martin
authors.affiliation: Core Facilities, Medical University of Vienna, Austria.
authors.forename: Marion
authors.initials: M
authors.lastname: Gröger
authors.affiliation: Department of Internal Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Austria.
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
authors.affiliation: Ludwig Boltzmann Institute of Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria.|Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holnthoner
authors.affiliation: Department of Obstetrics, Medical University of Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eppel
authors.affiliation: Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Neumayer
authors.affiliation: Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria.
authors.forename: Ihor
authors.initials: I
authors.lastname: Huk
authors.affiliation: 3rd Medical Department for Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Austria.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Demyanets
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Austria.|Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria.|Core Facilities, Medical University of Vienna, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
mesh_terms: D001777:Blood Coagulation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D000067596:Interleukin-33 / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D013925:Thromboplastin / Q000096:biosynthesis*
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D012333:RNA, Messenger; D013925:Thromboplastin