FIGURE 1.

Role of endothelial glycocalyx and platelets in vascular injury. Glycocalyx lines the vascular endothelial cell surface facing the vessel lumen forming a barrier between blood and endothelium maintaining the steady state, but also protects vasculature from pathogens. Glycocalyx supports anticoagulation by enhancing the natural anticoagulants antithrombin (AT), tissue factor pathway inhibitor (TFPI), protein C and S. Disruption of the glycocalyx exposes endothelial cell adhesion molecules [endothelial cell intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin] and extracellular matrix components, i.e., von Willebrand factor (VWF), collagen and tissue factor (TF) in a deeper injury (smooth muscle cells, adventitia). These structures capture blood cells, activating the crosstalk between the inflammatory cells and the coagulation system. Activated platelets release heparinase, metalloproteinases and collagenase to progress the local injury. Activation of platelets feeds back further expression of procoagulant P-selectin, platelet factor 4 (PF4), interleukin-1β (IL-1β), and CD40 ligand to foster the thrombo-inflammatory interactions. Enhanced activation of platelets and leukocytes induces neutrophil extracellular traps (NETs) formation, which in turn activates both inflammatory and hemostatic arms. Vascular endothelial injury and related procoagulant and inflammatory activities may be downplayed by replacing the defective glycocalyx structure with glycosaminoglycan (GAG) moieties, such as APAC.