Prothrombotic Effects of Fibronectin Isoforms Containing the EDA Domain
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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.
Methods and 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 μm) grew faster when compared with EDAWT/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 EDAWT/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.