BackgroundEndothelial proteinC receptor (EPCR) must be bound to a molecule of phosphatidylcholine (PC) to be fully functional, i.e. to interact with proteinC/activated proteinC (APC) properly. PC can be replaced with other lipids, such as lysophosphatidylcholine or platelet-activating factor, by the action of groupV secretory phospholipaseA2 (sPLA2-V), an enzyme that is upregulated in a variety of inflammatory conditions. Studies in purified systems have demonstrated that the substitution of PC notably impairs EPCR function in a process called EPCR encryption. ObjectivesTo analyze whether sPLA2-V was able to regulate EPCR-dependent proteinC activation invivo, and its impact on thrombosis and the hemostatic system. MethodsMice were transfected with sPLA2-V by hydrodynamic gene delivery. The effects on thrombosis were studied with the laser carotid artery occlusion model, and APC generation capacity was measured with ELISA. Global hemostasis was analyzed with thromboelastometry. ResultsWe found that sPLA2-V overexpression in mice significantly decreased their ability to generate APC. Furthermore, a murine carotid artery laser thrombosis model revealed that higher sPLA2-V levels were directly associated with faster artery thrombosis. ConclusionssPLA2-V plays a thrombogenic role by impairing the ability of EPCR to promote proteinC activation.