Endothelial cell control of thrombosis

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.

Endothelial Dysfunction and Venous Thrombosis

“…12 Reduced venous wall shear stress induces hypoxia and stimulates release of P-selectin and von Willebrand factor (vWF) from endothelial cells thus promoting thrombus formation. 13 Once the endothelial cells become activated they play an essential role in the generation of thrombin through the expression of procoagulant factors that contribute to both the initiation and propagation of thrombus generation.…”

Platelet-mimetic strategies for modulating the wound environment and inflammatory responses

“…Nandi and Brown Platelet-mimetic strategies for modulating the wound environment 1139 of a fibrin clot. 7 These events occur alongside primary hemostasis, but rather than facilitating platelet aggregation, they induce the formation of an insoluble fibrin clot through the binding of the pro-coagulant tissue factor (TF) molecule to coagulation factor fVII, forming a TF/fVII complex that can cleave factorX into factorXa, a molecule that generates thrombin. Thrombin activates the adherent platelet aggregate, allowing several other pro-coagulant factors to bind to the surface of the aggregate.…”

“…10,12 The fibrin mesh and platelet aggregate form a complete clot that can prevent further blood loss. 7,13 Following the cessation of bleeding, cytoplasmic motility proteins, including actin and myosin, facilitate platelet clot contraction, resulting in expulsion of serum from the clot. 14 The contractile forces generated by the platelet-rich plasma within the clot increases with time, forming a seal at the clot site to fortify the hemostatic capabilities of the clot.…”

“…During primary hemostasis, platelets target and aggregate at the injury site to form a ''plug'' of sorts. 7 Platelets bind to exposed sub-endothelial collagen at the injury site via the von Willebrand factor (VWF), which is released from the Weibel-Palade bodies of injured vessel walls. 8 The A1 domain of the secreted VWF interacts with GPIba, a ligand-binding protein within the glycoprotein GP-Ib-V-IX complex on the platelet's surface, allowing the platelets to adhere to the damaged vascular wall.…”

Clinical Significance of Peripheral Endothelial Function for Left Atrial Blood Stagnation in Nonvalvular Atrial Fibrillation Patients With Low-to-Intermediate Stroke Risk

“…21 Impairment of endothelial function triggers the platelet adhesion and aggregation, and fibrin formation that play a critical role in systematic hypercoagulability. Several recent reports suggested that endothelial NOS downregulation in the LA was associated with the development of LA thrombi formation even in the presence of sinus rhythm.…”