title: Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall.
abstract: Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF(-/-), hTF-Tg+, or "low-TF") demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA. sday@umich.edu
authors.forename: Sharlene M
authors.initials: SM
authors.lastname: Day
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reeve
authors.forename: Brian
authors.initials: B
authors.lastname: Pedersen
authors.forename: Diana M
authors.initials: DM
authors.lastname: Farris
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Myers
authors.forename: Michael
authors.initials: M
authors.lastname: Im
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Wakefield
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
authors.forename: William P
authors.initials: WP
authors.lastname: Fay
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D001808:Blood Vessels / Q000166:cytology* / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004910:Erythrocyte Membrane / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D017353:Gene Deletion; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013925:Thromboplastin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D013925:Thromboplastin; D015951:Factor Xa