Cellular fibronectin containing extra domain A promotes arterial thrombosis in mice through platelet Toll-like receptor 4

Abstract

Cellular fibronectin containing extra domain A (Fn-EDA1), which is produced in response to tissue injury in several disease states, has prothrombotic activity and is known to interact with Toll-like-receptor 4 (TLR4). The underlying mechanism and cell types involved in mediating the prothrombotic effect of Fn-EDA+ still remain unknown. Using intravital microscopy, we evaluated susceptibility to carotid artery thrombosis after FeCl3-induced injury in mice expressing Fn lacking EDA (Fn-EDA-/- mice) or Fn containing EDA (Fn-EDA+/+ mice). Fn-EDA-/- mice exhibited prolonged times to first thrombus formation and complete occlusion and a significant decrease in the rate of thrombus growth (P