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Two to tango: endothelial cell TMEM16 scramblases drive coagulation and thrombosis
János G. Filep
János G. Filep
Published June 1, 2023
Citation Information: J Clin Invest. 2023;133(11):e170643. https://doi.org/10.1172/JCI170643.
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Two to tango: endothelial cell TMEM16 scramblases drive coagulation and thrombosis

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Abstract

Endothelial cells form a constitutively anticoagulant surface under homeostasis. While loss of this anticoagulant property is a hallmark of many cardiovascular diseases, the molecular mechanisms underlying the procoagulant transition remain incompletely understood. In this issue of the JCI, Schmaier et al. identify the phospholipid scramblases TMEM16E and TMEM16F, which support endothelial procoagulant activity through phosphatidylserine (PS) externalization. Genetic deletion of TMEM16E or TMEM16F or treatment with TMEM16 inhibitors prevented PS externalization and reduced fibrin formation in the vessel wall independently of platelets in a murine laser-injury model of thrombosis. These findings reveal a role for endothelial TMEM16E in thrombosis and identify TMEM16E as a potential therapeutic target for preventing thrombus formation.

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János G. Filep

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