title: Myeloid cell tissue factor does not contribute to venous thrombogenesis in an electrolytic injury model.
abstract: BACKGROUND
  Tissue factor (TF) is a potent initiator of the extrinsic coagulation cascade. The role and source of TF in venous thrombotic disease is not clearly defined. Our study objective was to identify the contribution of myeloid cell TF to venous thrombogenesis in mice.
  
  
  METHODS
  The mouse electrolytic inferior vena cava model was used to induce thrombosis. The following groups of mice were used (1) TF(flox/flox)LysMCre(+) mice that have reduced TF expression in myeloid cells, (2) TF(flox/flox)LysMCre(-) littermate controls, (3) Wild type mice given a monoclonal anti-mouse TF antibody (1H1) to inhibit TF activity, and (4) Wild type mice given rat IgG. Evaluations at baseline, day 2, and day 6 post thrombosis included thrombus weight, vein wall inflammatory cell migration, vein wall TF mRNA, and plasma D-dimer levels.
  
  
  RESULTS
  Inhibition of TF significantly decreased thrombus weight 2days post venous thrombosis. In contrast, TF(flox/flox)LysMCre(+) had no change in thrombus weight when compared to littermate controls. The absence of myeloid cell TF did not affect infiltration of neutrophils or monocytes into the vein wall. TF mRNA expression in the vein wall decreased at 2days but then returned to baseline levels by 6days post thrombosis. D-dimer levels peaked at 2days post thrombosis in mice with or without myeloid cell TF.
  
  
  CONCLUSIONS
  TF is important in the formation of venous thrombi in the macrovasculature. However, TF expression by myeloid cells does not significantly contribute to venous thrombogenesis in this model.
authors.affiliation: Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, Michigan, USA; Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Hampton
authors.forename: Jose A
authors.initials: JA
authors.lastname: Diaz
authors.forename: Angela E
authors.initials: AE
authors.lastname: Hawley
authors.forename: Shirley K
authors.initials: SK
authors.lastname: Wrobleski
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wang
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Lee
authors.forename: Daniel
authors.initials: D
authors.lastname: Kirchhofer
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sigler
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Wakefield
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Myers
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014682:Vena Cava, Inferior / Q000378:metabolism / Q000473:pathology; D020246:Venous Thrombosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D012333:RNA, Messenger; C036309:fibrin fragment D; D013925:Thromboplastin