Medical device for the prevention of thrombosis

Abstract

The presently disclosed subject matter provides a mechanism in which DVTs form when reduced muscular activity results in loss of oscillatory shear-dependent transcriptional and ant-thrombotic phenotypes in peri-valvular venous endothelial cells. Endothelial cells surrounding the venous valve, where DVTs originate, experience oscillatory shear forces in response to muscular activity. Peri-valvular venous endothelial cells express high levels of FOXC2 and PROX1, transcription factors known to be activated by oscillatory shear stress, exhibit an anti-thrombotic phenotype characterized by low levels of the procoagulant proteins von Willebrands Factor (vWF), P-selectin and intercellular adhesion molecule 1 (ICAM1), high levels of the anticoagulant proteins thrombomodulin (THBD), endothelial protein C receptor (EPCR) and tissue factor pathway inhibitor (TFPI), and resistance to thrombin-induced clot formation. The peri-valvular venous anti-thrombotic endothelial phenotype is lost following femoral artery ligation that reduces venous flow or genetic loss of FOXC2 or PROX1 in mice, and at the site of human DVT associated with lethal PE.

Dependencies are inferred from the claim text.