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Group V secretory phospholipase A 2 impairs endothelial protein C receptor‐dependent protein C activation and accelerates thrombosis in vivo
Author(s) -
Tamayo I.,
Velasco S. E.,
Puy C.,
Esmon C. T.,
Dichiara M. G.,
Montes R.,
Hermida J.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12676
Subject(s) - hemostasis , protein c , in vivo , chemistry , platelet , microbiology and biotechnology , immunology , biology , medicine , biochemistry
Summary Background Endothelial protein C receptor (EPCR) must be bound to a molecule of phosphatidylcholine (PC) to be fully functional, i.e. to interact with protein C/activated protein C (APC) properly. PC can be replaced with other lipids, such as lysophosphatidylcholine or platelet‐activating factor, by the action of group V secretory phospholipase A2 ( sPLA 2‐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. Objectives To analyze whether sPLA 2‐V was able to regulate EPCR‐dependent protein C activation in vivo , and its impact on thrombosis and the hemostatic system. Methods Mice were transfected with sPLA 2‐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. Results We found that sPLA 2‐V overexpression in mice significantly decreased their ability to generate APC. Furthermore, a murine carotid artery laser thrombosis model revealed that higher sPLA 2‐V levels were directly associated with faster artery thrombosis. Conclusions sPLA 2‐V plays a thrombogenic role by impairing the ability of EPCR to promote protein C activation.