Abstract
Hemostasis encompasses a set of tightly regulated processes that govern blood clotting, platelet activation, and vascular repair. Upon vascular injury, the hemostatic system initiates a series of vascular events and activates extravascular receptors that act in concert to seal off the damage. Blood clotting is subsequently attenuated by a plethora of inhibitors that prevent excessive clot formation and eventual thrombosis. The endothelium which resides at the interface between the blood and surrounding tissues, serves an integral role in the hemostatic system. Depending on specific tissue needs and local stresses, endothelial cells are capable of evoking either antithrombotic or prothrombotic events. Healthy endothelial cells express antiplatelet and anticoagulant agents that prevent platelet aggregation and fibrin formation, respectively. In the face of endothelial dysfunction, endothelial cells trigger fibrin formation, as well as platelet adhesion and aggregation. Finally, endothelial cells release pro-fibrinolytic agents that initiate fibrinolysis to degrade the clot. Taken together, a functional endothelium is essential to maintain hemostasis and prevent thrombosis. Thus, a greater understanding into the role of the endothelium can provide new avenues for exploration and novel therapies for the management of thromboembolisms.
Highlights
The endothelium has been described as a cellophane type barrier that separates the blood from the surrounding tissue
Since the endothelium is located at the nexus of hemostasis and thrombosis, a clear understanding of how endothelialderived molecules contribute to hemostasis and thrombosis is vital for the identification of potential therapeutic targets and design of novel therapies for acute thrombosis
Hepatocyte-specific deletion of Lman1 in mice did not reveal any effect on plasma fVIII levels, supporting the observation that fVIII is synthesized in multiple types of endothelial cells. These results provide solid evidence that endothelial cells are the primary source of fVIII
Summary
The endothelium has been described as a cellophane type barrier that separates the blood from the surrounding tissue. The luminal surface of the endothelium expresses a plethora of molecules that regulate the activation of platelets and the coagulation cascade, thereby maintaining blood flow and preventing thrombus formation after vessel injury [9, 10]. Once endothelial cells become activated, they play an essential role to the generation of thrombin through expression of pro-coagulant factors that contribute to both initiation and propagation of thrombin generation.
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