THROMBIN-INDUCED ENDOTHELIAL-CELL DYSFUNCTION

Endothelium is a multifunctional organ which can directly influence circulating blood components as well as other cells within the vessel wall. The clotting enzyme thrombin, generated at the surface of damaged endothelium, induces blood coagulation but also exerts a variety of functional effects on the endothelium itself. Thrombin acts on endothelial cells to stimulate synthesis and release of various agents, such as inflammatory mediators, vasoactive substances and growth factors. It causes leukocyte adhesion to the endothelium by triggering expression of adhesion molecules on the cell surface and causes disruption of endothelial permeability properties. The majority of thrombin effects on endothelial cells are mediated by its receptor and require its lytic activity. Differences have been observed among the response to thrombin of endothelial cells of different origin. In general microvascular endothelial cells appear to be particularly sensitive to this enzyme. Thrombin induced microvascular dysfunction can have pathological consequences and contribute to organ reactions to inflammation and ischaemia.