Abstract 10824: A Novel Role of Endothelial Autophagy in the Regulation of Thrombosis in vivo

Background: Arterial thrombosis of native and graft vessels is the inciting event for acute coronary syndromes, and the cause of significant cardiovascular morbidity and mortality. Endothelial cell (EC) dysfunction is believed to play a central role in the pathobiology of thrombosis. ECs are activated upon atherosclerotic plaque rupture and induce the expression of tissue factor (TF) with resultant atherothrombotic sequelae. The molecular basis of how endothelial TF is unregulated remains unknown. We hypothesize that endothelial autophagy, a process involved in cellular homeostasis and stress responses, plays a causal role in the expression of TF, and via this mechanism modulates thrombosis. Methods: We generated EC-specific ATG7 knockout (EC-ATG7-/-) mice using CreLoxP technology. We used small interfering RNA (siRNA) to knockdown and characterize the effect of ATG7 inhibition in HUVECs. We also employed intravital microscopy in FeCl3-induced carotid and laser-induced cremaster artery injury to evaluate ...