FIGURE 2. Pivotal role of the endothelial cells in hemostasis, thrombosis and fibrinolysis.


Pivotal role of the endothelial cells in hemostasis, thrombosis and fibrinolysis. Upper panel: In normal conditions, endothelial cells show an anti-thrombotic phenotype [degradation of the aggregating agent ADP with ectonucleotidases; prevention of primary hemostasis: i.e., platelet activation, adhesion and aggregation, by expressing 13-hydroxyoctadecadienoic acid (13-HODE), and releasing prostacyclin (PGI2), and NO], an anticoagulant phenotype [expression of the thrombin receptor thrombomodulin and the protein C/S system, which converts thrombin from a procoagulant to an anticoagulant enzyme; expression of the tissue factor pathway inhibitor and the binding/activation of anti-thrombin to cell surface heparin-like molecules such as glycosaminoglycans (heparan sulfate)] and a pro-fibrinolytic phenotype [release of tissue-type plasminogen activator (t-PA) and possibly urokinase-type plasminogen activator (u-PA)]. Lower panel: Following vascular injury and under pathological conditions, the endothelium shifts to a pro-thrombotic/pro-coagulant phenotype, by releasing the von Willebrand factor (vWF), thromboxane A2 (TXA2) and platelet-activating factor (PAF), synthesized via the remodeling pathway, which play a major role in initial platelet recruitment and thrombus formation, by expressing the thrombin receptor protease-activated receptor-1 (PAR-1), which enhances the release of vWF and reinforces endothelial cell activation, for instance, by promoting the expression of adhesion molecules to the cell surface (ICAM-1, VCAM-1, E-selectin, P-selectin), and by producing plasminogen activator inhibitor type-I (PAI-1), which prevents fibrinolysis by inhibiting t-PA (and u-PA) activity. ADP: adenosine diphosphate; AMP: adenosine monophosphate; COX: cyclooxygenase; NOS: nitric oxide synthase; PLA2: phospholipase A; EC2.3.1.67: acetyl-CoA:2-lyso-PAF acetyltransferase.

From: Chapter 2, Multiple Functions of the Endothelial Cells

Cover of The Endothelium
The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators.
Félétou M.
San Rafael (CA): Morgan & Claypool Life Sciences; 2011.
Copyright © 2011 by Morgan & Claypool Life Sciences Publishers.

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