On the miscellaneous aspects of von Willebrand factor

Abstract

Von Willebrand disease is the most common inherited bleeding disorder and is characterized by reduced plasma von Willebrand factor (VWF) levels or functionally abnormal VWF. VWF is best known for its three classical hemostatic functions: (i) as a carrier protein for coagulation factor VIII, (ii) binding to exposed collagen upon vascular damage and (iii) as a mediator of the recruitment of platelets to sites of vascular injury. However, in recent years it has become clear that VWF has a versatile function beyond hemostasis, and has been implicated in several pathophysiological processes, such as tumor metastasis, angiogenesis, cell proliferation and inflammatory processes. So, apart from its evident role in hemostasis, it has become clear that VWF is a much more complex multifaceted protein then initially thought. Several aspects __ from synthesis, secretion and clearance, to functions in the circulation __ of this protein have been studied and the results are described in this thesis. These results will advance our knowledge about the mechanism(s) of VWF biosynthesis, clearance and its role in angiogenesis, which might lead to a more personalized treatment for von Willebrand disease and its complications in the future.