von Willebrand factor and inflammation

Abstract

Von Willebrand factor (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 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. In return, 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, evidence of a link between VWF and inflammation arose much earlier than these recent developments. At first, VWF was considered only as a marker of inflammation in various pathologies, due to its acute release by the activated endothelium. Later on, 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 inflammation players such as P-selectin. Finally, 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 will attract leukocytes. This review will focus on these different aspects of the connection between VWF and inflammation, with particular emphasis on VWF-leukocyte interactions.

Investigation of changes in vWF expression in rabbit carotid artery collar model

“…vWF'de vasküler inflamasyonun göstergelerinden biridir (3,17) ve giriş bölümünde değindiğimiz gibi yaka modelinde vWF varlığı ve ekspresyon düzeyle-rinde artış daha önce yapılan çalışmalarda da bildirilmiştir (4,13) . Çalışmamızda da elde ettiğimiz bulgular bunu desteklemektedir.…”

“…von Willebrand faktör üzerine yapılan çalışmalar bu proteinin tromboz dışında inme, ateroskleroz gibi pek çok farklı süreçte de rol aldığını göstermektedir (15,16) . İnflamasyon ve vWF faktör arasındaki ilişki uzun yıllardır bilinmektedir ve farklı inflamasyon süreçlerinde pek çok direkt ve indirek rolleri vardır (17) . vWF vasküler hasarda önemli bir rol oynar (15,17) .…”

“…İnflamasyon ve vWF faktör arasındaki ilişki uzun yıllardır bilinmektedir ve farklı inflamasyon süreçlerinde pek çok direkt ve indirek rolleri vardır (17) . vWF vasküler hasarda önemli bir rol oynar (15,17) . vWF'ün polimorfonükleer lökositler ile etkileştiği ve vWF aracılı lökosit adezyonunun P-selektin için ligand görevi gördüğü göste-rilmiştir (18) .…”

Recombinant human ADAMTS13 treatment and anti-NET strategies enhance skin allograft survival in mice

“…In addition to alloimmunity conferred by activated lymphocytes, microthrombosis may also be a key factor contributing to allograft rejection . ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is a plasma metalloproteinase that cleaves ultralarge von Willebrand factor (UL‐VWF), which is highly proinflammatory and pro‐thrombotic . Patients receiving liver transplants had significantly reduced plasma ADAMTS13 activity and elevated levels of UL‐VWF multimers in the circulation .…”

Mice deficient in the anti-haemophilic coagulation factor VIII show increased von Willebrand factor plasma levels

“…By tissue-specific gene targeting approaches it was recently demonstrated not only to be synthesized in, but also stored together with von Willebrand Factor (VWF) in Weibel-Palade bodies of liver endothelial cells [8, 9]. As a marker of endothelial cell activation, plasma VWF is an established endothelial acute-phase response protein with adhesive properties to leukocytes and recognized roles in leukocyte recruitment in different vascular inflammatory diseases [10–12]. While VWF is well-recognized as the carrier molecule of FVIII in plasma, stabilizing FVIII activity by preventing proteolytic degradation [13, 14], the possible impact of FVIII on VWF plasma levels is poorly resolved.…”