The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy

Figure 1

Functional heterogeneity of von Willebrand factor (VWF). VWF is best known for its role in hemostasis and thrombosis, supporting platelet adhesion/aggregation and protecting FVIII from proteolytic degradation in blood flow. However, it is now clear that VWF functions extend much further than that. VWF plays a key role in vascular inflammation, favoring leukocyte recruitment and extravasation, activating complement cascade, and participating in NETosis. In cardiovascular disease, including CAD and stroke, VWF is a predictor of future CV events. In atherosclerosis, VWF promotes plaque formation and inflammation in animal models. An increase in VWF activity or ADAMTS13 deficiency may result in microvascular obstruction and thrombotic microangiopathy (TMA). In sepsis, inflammatory and infective stimuli may induce an acute imbalance in the VWF/ADAMTS13 ratio with possible thrombotic complications (i.e., DIC). Finally, a growing interest is emerging on selective VWF antagonism as a new therapeutic option to provide a further advance in the treatment of thrombotic and inflammatory disorders. VWF: von Willebrand factor; ADAMTS13: a disintegrin and metalloprotease with the thrombospondin motif; TMA: thrombotic microangiopathy; CV: cardiovascular; CAD: coronary artery disease; TTP: thrombotic thrombocytopenic purpura; HUS: hemolytic uremic syndrome.