Protease‐activated receptors‐1 and ‐2 can mediate endothelial barrier protection: role in factor Xa signaling

摘要: Summary.  Coagulation and inflammation are intimately linked cellular signaling by coagulation proteases through protease-activated receptors (PARs) may affect pro- anti-inflammatory responses. Permeability of the endothelial cell barrier at blood–tissue interface plays a key role in inflammatory disorders such as sepsis. We have recently shown that PAR1 activated protein C or low concentrations thrombin can enhance integrity. In present study, we analyzed effects factor Xa (FXa), which is known to activate both PAR2, on monolayer integrity using transformed human umbilical vein (HUVEC) line dual-chamber system. Preincubation with FXa potently reduced high-dose thrombin-mediated hyperpermeability basal permeability. was protective 5 nm higher proteolytic activity required. Barrier not affected cleavage-blocking anti-PAR1 antibodies antagonist. Similarly, anti-PAR2 alone had no effect, but blocking PAR2 inhibited protection FXa. Incubation layer PAR2-specific agonist peptide permeability similar conclusion, only PAR1, also mediate cells use either receptor Although it currently unknown whether PAR has physiological role, results suggest potential effect other agonists should be explored models local systemic vivo.