The protein C pathways

To provide an overview of the state-of-the-art in protein C (PC) pathway research.The PC pathway is crucial for maintaining hemostasis to prevent venous thromboembolism. This is evident from genetic mutations that result in impaired PC pathway activity and contribute to increased venous thromboembolism risk in affected individuals. In addition to its anticoagulant role, activated PC (APC) also mediates a complex, pleiotropic role in the maintenance of vascular cell health, which it achieves via anti-inflammatory and antiapoptotic cell signaling on endothelial cells. Emerging data have demonstrated that cell signaling by APC, mediated by multiple receptor interactions on different cell types, also confers cytoprotective and anti-inflammatory benefits. Defects in both arms of the PC pathway are associated with increased susceptibility to thrombo-inflammatory disease in various preclinical thrombotic, proinflammatory and neurological disease models. Moreover, recent studies have identified attenuation of anticoagulant PC pathway activity as an exciting therapeutic opportunity to promote hemostasis in patients with inherited or acquired bleeding disorders.In this review, we provide an overview of some recent developments in our understanding of the PC pathways.