دورية أكاديمية
Group V secretory phospholipase A2 impairs endothelial protein C receptor-dependent protein C activation and accelerates thrombosis in vivo.
| العنوان: | Group V secretory phospholipase A2 impairs endothelial protein C receptor-dependent protein C activation and accelerates thrombosis in vivo. |
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| المؤلفون: | Tamayo I; Division of Cardiovascular Sciences, Laboratory of Thrombosis and Hemostasis, Center for Applied Medical Research, University of Navarra, Pamplona, Spain., Velasco SE, Puy C, Esmon CT, Dichiara MG, Montes R, Hermida J |
| المصدر: | Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2014 Nov; Vol. 12 (11), pp. 1921-7. Date of Electronic Publication: 2014 Oct 12. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 101170508 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7836 (Electronic) Linking ISSN: 15387836 NLM ISO Abbreviation: J Thromb Haemost Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : [New York] : Elsevier Original Publication: Oxford : Blackwell Pub. |
| مواضيع طبية MeSH: | Carotid Stenosis/*enzymology , Group V Phospholipases A2/*biosynthesis , Liver/*enzymology , Protein C/*metabolism , Receptors, Cell Surface/*metabolism , Thrombosis/*enzymology, Animals ; Carotid Stenosis/blood ; Carotid Stenosis/genetics ; Disease Models, Animal ; Endothelial Protein C Receptor ; Enzyme Activation ; Enzyme Induction ; Enzyme Inhibitors/pharmacology ; Gene Transfer Techniques ; Group V Phospholipases A2/antagonists & inhibitors ; Group V Phospholipases A2/genetics ; Hemostasis ; Humans ; Liver/drug effects ; Mice, Inbred ICR ; Signal Transduction ; Thrombosis/blood ; Thrombosis/genetics ; Time Factors |
| مستخلص: | 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 (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. Objectives: To analyze whether sPLA2-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 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. Results: We 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. Conclusions: sPLA2-V plays a thrombogenic role by impairing the ability of EPCR to promote protein C activation. (© 2014 International Society on Thrombosis and Haemostasis.) |
| التعليقات: | Comment in: J Thromb Haemost. 2014 Nov;12(11):1918-20. (PMID: 25224632) |
| فهرسة مساهمة: | Keywords: activated protein C resistance; endothelial cell protein C receptor; group V secretory phospholipase A2; protein C; thrombosis |
| المشرفين على المادة: | 0 (Endothelial Protein C Receptor) 0 (Enzyme Inhibitors) 0 (Procr protein, mouse) 0 (Protein C) 0 (Receptors, Cell Surface) EC 3.1.1.4 (Group V Phospholipases A2) EC 3.1.1.4 (PLA2G5 protein, human) |
| تواريخ الأحداث: | Date Created: 20140730 Date Completed: 20151015 Latest Revision: 20230829 |
| رمز التحديث: | 20230830 |
| DOI: | 10.1111/jth.12676 |
| PMID: | 25069533 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1538-7836 |
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| DOI: | 10.1111/jth.12676 |