Thrombotic Regulation From the Endothelial Cell Perspectives
Thrombosis, the localized clotting of blood that affects arterial or venous circulation, is one of the leading causes of death worldwide.1 Currently used antithrombotic drugs have increased bleeding risk.2,3 Exploring new antithrombotic strategies that preserve physiological hemostasis is under intensive investigation. Classical triad of causative factors leading to thrombosis includes alterations in blood content, alterations in blood flow, and alterations in the vessel wall. Endothelium, the inner most single layer of cells lining the blood vessels, provides a surface for thrombosis formation and critically regulates blood fluidity and homeostasis. As barrier, endothelium separates blood clotting factors from exposure to subendothelial prothrombotic extracellular matrix components. Endothelium also secretes or expresses vasoactive factors that modulate platelet reactivity, coagulation, fibrinolysis, and vascular contractility, all of which contribute to thrombotic formation. Such factors include nitric oxide, prostacyclin, Von Willebrand factor (VWF), thrombomodulin, endothelin, etc. Accumulating evidences show that endothelial cells (ECs) play a pivotal role in modulating thrombosis, highlighting ECs as a potential target for thrombosis control. In this Recent Highlights, we reviewed recent publications in Arteriosclerosis, Thrombosis, and Vascular Biology and other leading journals that are focused on the mechanisms of endothelial regulation of thrombosis and discussed their merits in therapeutic discovery.
Arterial thrombosis is commonly initiated by vascular endothelial erosions and ruptures of an atherosclerotic plaque3,4 while venous thrombosis mainly stems from blood stasis.5 Despite these differences, platelet adhesion/activation, and fibrin deposition as the result of coagulation constitute the fundamental processes of thrombus formation.6,7 Platelet activation occurs when they interact with activated ECs (with increased VWF release and selectin expression) via glycoprotein Ib-V-IX complex binding to VWF, or when they expose to subendothelial extracellular matrix components, such as collagen (via glycoprotein VI receptor), in the cases of endothelial injury or plaques …