Abstract
Recent studies established a novel mouse model of deep vein thrombosis (DVT) induced by flow restriction, closely resembling the time course and histological features of DVT in humans. Detailed analysis of this model revealed that venous thrombi were formed by more elegant biological reactions than expected. In this model, the compromised venous blood flow induced endothelial cell activation initiating expression of adhesive ligands and generation of inflammatory cytokines, resulting in recruitment of monocytes, neutrophils, and platelets. Recruited monocytes trigger the extrinsic coagulation cascade via monocyte-derived tissue factor. Neutrophils released their nuclear substances decorated with granular proteins (NETs) which in turn trigger the FXII-initiated intrinsic coagulation cascade. Platelets support leukocyte accumulation and strongly promote NETs formation. These findings suggest that inhibition of FXII and NETs may be promising strategies for the treatment of DVT. Unraveling the molecular mechanism of DVT would help better understanding of the characteristics of current anti-thrombotic drugs and pave the way to the development of novel anti-thrombotic drugs with selective and safe profiles.
