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

Figure 3

VWF-mediated thromboinflammation in high-shear conditions. At high shear rates (e.g., arterioles, microcirculation, and artery stenosis), the inactive globular-shaped VWF rapidly unfolds and elongates in a highly reactive long-chain conformation. The elongated VWF can bind to platelets (a), allowing them to roll and adhere to the damaged endothelial surface. Platelet-decorated UL-VWF strings on activated endothelium represent a solid anchoring matrix for leukocyte adhesion (b), so permitting leukocyte recruitment in the inflamed site. In the bloodstream, VWF also binds to “neutrophil extracellular traps” (NETs) (c), inflammatory mediators (decondensed nucleosomes, extracellular DNA, and proteins) released by activated neutrophils, creating a network able to recruit both platelets and leukocytes and to promote thrombus formation.