Endothelial Cell Injury Induces Microcirculation Disturbances

On the surface of endothelial cells, there are three kinds of anticoagulant systems (Figure 1). First, a heparin-like substance, glycosaminoglycan (GAG), covers the endothelial cell surface. GAG is a receptor for antithrombin and promotes its antithrombotic property. Thrombin and antithrombin both have an affinity for GAG and the inhibitory reaction is accelerated by GAG. In ALI, inflammatory mediators such as neutrophil elastase cleave GAG

and the endothelial GAG content decreases severely. Second, thrombomodulin is another anticoagulant protein on the endothelial cells. When thrombin is formed in the blood circulation, it binds to thrombomodulin. Once thrombin binds to thrombomodulin, its procoagulant potential is converted into anticoagulant and it activates a physiologic anticoagulant called protein C. Activated protein C inhibits the active forms of coagulation factors V and VIII so that thrombomodulin-thrombin complexes inhibit further thrombus formation. In the case of ALI, cytokines such as TNF or IL-1 activate endothelial cells and downregulate the thrombomodulin expression (Figure 1). Neutrophil elastase also damages thrombomodulin. Third, prostaglandin I2 (PGI2) and NO are produced from the endothelial cells and regulate platelet aggregation and vascular smooth muscle cell contraction (Figure 1). NO, which regulates proper vascular tone, is mainly produced by eNOS. In ALI or severe inflammatory diseases, endothelial production of PGI2 and the activity of eNOS decrease. In addition to these losses of anticoagulant potential in endothelial cells, cytokine-activated endothelial cells express tissue factor, which stimulates the coagulation cascade. Taken together, micro-thrombi are easily formed in the pulmonary microcirculation and interrupt smooth blood flow.

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Essentials of Human Physiology

Essentials of Human Physiology

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