On Monday, during the Joint ISTH-WFH Session on Novel Functions of Von Willebrand factor (VWF), Cecile Denis, M.D. discussed the importance of VWF in inflammation. Her presentation highlighted key points from an upcoming manuscript which will be published in the Journal of Thrombosis and Haemostasis:
- VWF plays an important hemostatic role following vascular injury, but is also recognized as a risk factor for both arterial and venous thrombosis.
- The link between hemostasis and inflammation is more nuanced than previously understood, and has been better defined recently.
- Among the actors involved in both processes, VWF serves complex and multiple roles, not only as a marker of inflammation but also as an active player in directing the biogenesis of specific endothelial organelles and recruiting leukocytes.
VWF is a plasma glycoprotein best known for its crucial hemostatic role in serving as a molecular bridge linking platelets to subendothelial components following vascular injury. In addition, VWF functions as a chaperone for coagulation factor VIII. In pathological settings, VWF is recognized as a risk factor for both arterial and venous thrombosis, as well as a molecular player that directly promotes the thrombotic process. Recent years have seen the emergence of the concept of immuno-thrombosis by which inflammatory cells participate in thrombotic processes. As such, reports about the involvement of hemostatic proteins or cells (such as platelets) in inflammatory responses have become increasingly common, emphasizing the intricate link between hemostasis and inflammation.
However, the link between VWF and inflammation has been appreciated well before the most recent developments were reported.
- At first, VWF was considered only as a marker of inflammation in various disease states, the result of its acute release by the activated endothelium.
- More recently, a more complex role of VWF in inflammation was uncovered, owing to its capacity to direct the biogenesis of specific endothelial organelles, the Weibel–Palade bodies, that contain known inflammatory mediators such as P-selectin.
- Most recently, a more direct link between VWF and inflammation has become apparent with the discovery that VWF is able to recruit leukocytes, either via direct leukocyte binding or by recruiting platelets, which in turn attract leukocytes.
The accumulation of VWF in skin biopsies of patients suffering from immune complex-mediated vasculitis favors a role for VWF in inflammation in humans. It would appear that in inflammation, the high-molecular multimers of VWF are of importance as ADAMTS13 plays an important role in downregulating the pro-inflammatory potential of VWF.
This review focuses on these different aspects of the connection between VWF and inflammation, with particular emphasis on VWF-leukocyte interactions.