Role of Endothelial Cells in Acute and Chronic Thrombosis

Abstract

Haemostasis encompasses a set of strictly regulated actions, such as vasoconstriction, platelet activation and blood coagulation. Endothelial cells play a crucial role in all of these processes and are an integral part of the vascular response to injury resulting in thrombus formation. Healthy endothelium expresses mediators to prevent platelet activation, including prostacyclin and nitric oxide, and to inhibit coagulation, such as thrombomodulin or RNase1. Upon activation, endothelial cells expose von Willebrand factor, integrins and other receptors to interact with activated platelets, erythrocytes and coagulation factors, respectively, resulting in blood clot formation. The endothelial cell response to cytokines and growth factors released from activated platelets and immune cells abundantly present in arterial and venous thrombi also plays an important role for thrombus resolution, whereas failure to completely resolve thrombi may initiate fibrotic remodelling and chronic vascular occlusion both in the arterial and venous tree. Therefore, endothelial cells are increasingly recognized as potential target to prevent thrombotic events and to accelerate thrombus resolution. Here, we discuss recent publications from our group in the context of other studies on the role of the endothelium during acute and chronic thrombotic events.

Zusammenfassung

Die Hämostase umfasst eine Reihe von streng regulierten Abläufen wie Vasokonstriktion, Thrombozytenaktivierung und Blutgerinnung. Endothelzellen spielen eine entscheidende Rolle in all diesen Prozessen und sind ein integraler Bestandteil der vaskulären Antwort auf Verletzungen, die zur Thrombusbildung führen. Gesundes Endothel exprimiert Mediatoren zur Verhinderung der Thrombozytenaktivierung einschließlich Prostacyclin und Stickoxid und zur Hemmung der Gerinnung, wie Thrombomodulin oder RNase1. Nach der Aktivierung exponieren Endothelzellen den von Willebrand-Faktor, Integrine und andere Rezeptoren, um mit aktivierten Thrombozyten, Erythrozyten bzw. Gerinnungsfaktoren zu interagieren, was zur Bildung von Blutgerinnseln führt. Die Endothelzellenantwort auf Cytokine und Wachstumsfaktoren, die von aktivierten Blutplättchen und Immunzellen in arteriellen und venösen Thromben freigesetzt werden, spielt ebenfalls eine wichtige Rolle bei der Thrombusauflösung, während eine unvollständige Auflösung von Thromben fibrotische Umbauprozesse und einen chronischen Gefäßverschluss sowohl im arteriellen als auch im venösen Bereich auslösen kann. Daher werden Endothelzellen zunehmend als potenzielles Ziel zur Vorbeugung thrombotischer Ereignisse und zur Beschleunigung der Thrombusauflösung erkannt. Hier diskutieren wir aktuelle Publikationen aus unserer Gruppe im Zusammenhang mit anderen Studien zur Rolle des Endothels bei akuten und chronischen thrombotischen Ereignissen.

Keywords

arterial - endothelial dysfunction - thrombosis - thrombus resolution - venous

Schlüsselwörter

arteriell - endotheliale Dysfunktion - Thrombose - Thrombusauflösung - venös

• References

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