Von Willebrand disease and Weibel-Palade bodies

Summary

Von Willebrand factor (VWF) is a pivotal haemostatic protein mediating platelet adhesion to injured endothelium and carrying coagulation factor VIII (FVIII) in the circulation to protect it from premature clearance. Apart from the roles in haemostasis, VWF drives the formation of the endothelial cell specific Weibel-Palade bodies (WPBs), which serve as a regulated storage of VWF and other thrombotic and inflammatory factors. Defects in VWF could lead to the bleeding disorder von Willebrand disease (VWD).

Extensive studies have shown that several mutations identified in VWD patients cause an intracellular retention of VWF. However, the effects of such mutations on the formation and function of its storage organelle are largely unknown. This review gives an overview on the role of VWF in WPB biogenesis and summarizes the limited data on the WPBs formed by VWD-causing mutant VWF.

Zusammenfassung

Der Von-Willebrand-Faktor (VWF) ist ein hämostatisches Schlüsselprotein, das die Plätt-chenadhäsion im verletzten Endothel vermittelt und im Blutkreislauf als Trägerprotein für den Gerinnungsfaktor VIII (FVIII) dient, um diesen vor dem vorzeitigen Abbau zu schüt-zen. Neben dieser Rolle in der Hämostase fördert der VWF außerdem die Bildung der für Endothelzellen spezifischen Weibel-Palade-Körperchen (WPK), die als geregelter Speicher für VWF und andere thrombotische und inflammatorische Faktoren dienen. Defekte im VWF können eine Gerinnungsstörung, das Von-Willebrand-Syndrom (VWS), auslösen. In umfassenden Studien wurde nachgewie-sen, dass verschiedene Mutationen, die bei Patienten mit VWS identifiziert wurden, eine intrazelluläre Retention des VWF verursachen können. Die Auswirkungen dieser Mutationen auf die Bildung und Funktion seiner Speicherorganellen sind jedoch weitgehend unbe-kannt. Dieser Übersichtsartikel gibt einen Überblick über die Rolle des VWF bei der Biogenese der WPK und fasst die wenigen Daten zu solchen WPK zusammen, die durch für das VWS verantwortliche VWF-Mutanten gebildet werden.

Keywords

Weibel-Palade body - von Willebrand factor - von Willebrand disease

Schlüsselwörter

Von-Willebrand-Erkrankung - von-Willebrand-Faktor - Weibel-Palade-Körperchen

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