Figure 4. Vitronectin is a substrate of PDI.

A.Vitronectin, a major plasma protein, does not bind to its receptors, endothelial ∝_vβ₃ and platelet ∝_IIbβ₃, under normal physiologic conditions. B. Vascular injury results in endothelial activation and release of PDI at the site of injury. Extracellular PDI reduces one or two disulfide bonds in vitronectin resulting in a structural change. C and D. ‘Activated’ vitronectin can now engage with its receptors ∝_vβ₃ and ∝_IIbβ₃ to support platelet aggregation and fibrin generation. The graphs show impaired platelet accumulation and fibrin generation at the site of vessel wall injury in the laser injury model of thrombus formation in vitronectin^−/− mice. The downstream substrates of vitronectin in thrombus formation remain elusive.