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The Endothelial protein C receptor (EPCR) is a Type I transmembrane glycoprotein primarily expressed on the surface of large vessel endothelial cells [1]. It plays a critical role in the protein C anticoagulant pathway by binding Protein C and presenting it to the thrombin-thrombomodulin complex, which significantly accelerates the generation of Activated Protein C (APC) [2]. In the context of xenotransplantation, human EPCR is expressed as a transgene on porcine endothelium to overcome molecular incompatibilities between pig and human coagulation systems, thereby preventing the rapid development of consumptive coagulopathy and thrombotic microangiopathy in the graft [3, 4]. Beyond its anticoagulant properties, the EPCR-APC complex triggers cytoprotective, anti-inflammatory, and anti-apoptotic signaling through the cleavage of Protease-activated receptor 1 (PAR-1) [2]. This dual role makes it a vital component in maintaining vascular integrity and regulating the host immune response during organ transplantation [4]. [1] UniProt (Q9UNN8); [2] PMID: 11069105; [3] PMID: 26458185; [4] PMID: 35045221.
EPCR binds Protein C and facilitates its activation by the thrombin-thrombomodulin complex on the endothelial surface. Once activated, Protein C (APC) dissociates or remains bound to EPCR to initiate cytoprotective signaling via PAR-1, which stabilizes the endothelial barrier and inhibits pro-inflammatory pathways [1, 2].
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