The Journal of thoracic and cardiovascular surgery

Endothelial-specific deletion of autophagy-related 7 (ATG7) attenuates arterial thrombosis in mice.

PMID 28400112


Thrombosis persists as a leading cause of morbidity and mortality. Given that endothelial cells (ECs) play a central role in regulating thrombosis, understanding the molecular endothelial cues that regulate susceptibility or resistance to thrombosis have important translational implications. Accordingly, we evaluated the role of endothelial autophagy in the development of thrombosis. We generated mice in which the essential autophagy-related 7 (ATG7) gene was conditionally deleted from ECs (EC-ATG7 We silenced ATG7 in HUVECs and observed >60% decreases in tumor necrosis factor (TNF)-α-induced tissue factor (TF) transcript levels, protein expression, and activity. TF mRNA levels in the carotid arteries of EC-ATG7 Taken together, these results provide definitive evidence that loss of endothelial ATG7 attenuates thrombosis and reduces the expression of TF. Our findings demonstrate that endothelial ATG7, and thus autophagy, is a critical and previously unrecognized target for modulating the susceptibility to thrombosis.