title: Prothrombotic effects of fibronectin isoforms containing the EDA domain.
abstract: OBJECTIVE
  Fibronectin (FN) plays an important role in the formation of stable arterial thrombi at the site of vascular injury. FN containing Extra Domain A (EDA+ FN) is absent from normal plasma, but elevated plasma levels of EDA+ FN are found in several pathological conditions. We hypothesized that EDA+ FN plays a special role in thrombosis.
  
  
  RESULTS
  We used mouse strains constitutively including (EDA+/+) or excluding (EDA-/-) the EDA domain in all tissues and plasma. Using a flow chamber and the ferric-chloride injury model we found that EDA+ FN accelerates thrombosis both in vitro and in vivo at arterial shear rates. In EDA+/+ mice thrombi (>30 microm) grew faster when compared with EDA(WT/WT) (6.6+/-0.2 minutes versus 8.3+/-0.6 minutes, P<0.05) and the mean vessel occlusion time was shorter (9.9+/-0.4 minutes versus 14.6+/-1.7 minutes, P<0.05). However, the presence of EDA+ FN affected neither single platelet adhesion to subendothelium nor thrombosis in veins. In addition, the mortality rate of EDA+/+ mice after collagen/epinephrine infusion was twice that of EDA(WT/WT) or EDA-/- mice.
  
  
  CONCLUSIONS
  Our findings reveal that EDA+ FN has prothrombotic activity, and its presence in plasma may worsen pathological conditions in which this form is elevated.
authors.affiliation: CBR Institute for Biomedical Research and the Department of Pathology, Harvard Medical School, Boston, Mass, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chauhan
authors.forename: Janka
authors.initials: J
authors.lastname: Kisucka
authors.forename: Maria R
authors.initials: MR
authors.lastname: Cozzi
authors.forename: Meghan T
authors.initials: MT
authors.lastname: Walsh
authors.forename: Federico A
authors.initials: FA
authors.lastname: Moretti
authors.forename: Monica
authors.initials: M
authors.lastname: Battiston
authors.forename: Mario
authors.initials: M
authors.lastname: Mazzucato
authors.forename: Luigi
authors.initials: L
authors.lastname: De Marco
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Baralle
authors.forename: Denisa D
authors.initials: DD
authors.lastname: Wagner
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Muro
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005353:Fibronectins / Q000737:chemistry* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015539:Platelet Activation / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D017434:Protein Structure, Tertiary; D011655:Pulmonary Embolism / Q000503:physiopathology*
chemical_list: D005353:Fibronectins; D020033:Protein Isoforms