Extracellular RNA. A new player in blood coagulation and vascular permeability

Upon vascular injury, locally controlled haemostasis prevents life threatening blood loss and ensures wound healing. Intracellular material derived from damaged cells at these sites will become exposed to cells and plasma proteins and could thereby influence vascular homeostasis, blood coagulation and defense mechanisms. Recently, this concept was documented by several studies indicating that extracellular nucleic acids, and RNA in particular, serve as promoter of blood coagulation in vivo and significantly increase the permeability across brain endothelial cells in vitro and in vivo. As procoagulant cofactor and "natural foreign material", RNA triggers the contactphase pathway of blood coagulation and thereby contributes to pathological thrombus formation. Administration of RNase significantly delayed occlusive thrombus formation and prevented edema formation in different animal models. Thus, extracellular RNA derived from damaged and necrotic cells may serve as a natural danger signal that contributes to initiation of host defense mechanisms, while antagonizing RNase provides new regimens for antithrombotic and vessel-protective therapies.