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 (EDAFN) is absent from normal plasma, but elevated plasma levels of EDAFN are found in several pathological conditions. We hypothesized that EDAFN 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 EDAFN accelerates thrombosis both in vitro and in vivo at arterial shear rates. In EDA mice thrombi (>30 μm) grew faster when compared with EDA (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 EDAFN 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 or EDA mice. CONCLUSIONS - Our findings reveal that EDAFN has prothrombotic activity, and its presence in plasma may worsen pathological conditions in which this form is elevated. © 2008 American Heart Association, Inc.