Endothelial thrombogenic/antithrombotic functions

The endothelium consists of a single-layered, non-cornifying squamous epithelium that lines the heart, blood and lymph vessels and acts as a selective barrier between the blood stream and the vessel wall for dissolved substances, macromolecules and cells. The endothelium actively controls the exchange between vascular lumen and interstitium. The endothelium plays a prominent role in the formation of wall-standing thrombi. This is especially true after endothelial integrity has been compromised.

Endothelial factors with thrombogenic:

• von Willebrand factor

• Thromboplastin( calledfactor III or tissue factor), an important activator of plasmatic coagulation from the subendothelium

• factor V

• PAF (Platelet activator factor)

• Factor XIV (high-molecular-weight-kininogen, HMWK, also called Fitzgerald factor)

• Collagen

• Plasminogen activator inhibitor-1 (PAI-1) = inhibitor of fribrinolysis.

The endothelium expresses receptors for:

• The HMWK

• The Tenase

• The prothrombinase

• The factors IX and X

• The von Willebrand factor

• The Fibrinogen

Via these receptors, the corresponding factors bind to the endothelium at the site of the lesion. The endothelium also binds fibrinogen, fibronectin and thrombin.

Endothelial factors with antithrombotic function:

In parallel to the thrombotic endothelial factors, antithrombotic mediators are also synthesized and activated in the endothelium:

• tissue factor pathway inhibitor (TFPI)

• Tissue plasminogen activator (t-PA), is synthesized and secreted in the endothelium

• Nitrogen monoxide (NO) = Anti-aggregation

• Prostacyclin (PGI2), which has an antiaggregatory effect and is stimulated by thrombin and noradrenalin, inhibits platelet activation

• ADPase, inhibits the activator ADP, a central stimulator of platelet aggregation

• Thrombomodulin which binds thrombin, thus changing its enzymatic specificity and thereby activating protein C

• Protein S (cofactor of protein C)

• Vasodilator-stimulated phosphoprotein

A further function for the anticoagulant effect of the endothelium results from the expression of receptors for:

• protein C

• Antithrombin III

In the case of injuries, the barrier between blood and subendothelial structures is broken. In this case, the subendothelial collagen induces platelet adhesion via the von Willebrand factor and finally its aggregation. Tissue factor = factor III) is released from the subendothelial tissue. In addition, macrophages, fibroblasts and muscle cells interact to induce plasmatic coagulation.

1. HA Neumann (2014) The coagulation system. ABW-Scientific Publisher GmbH Berlin