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Procoagulant Platelet Characterization by Measuring Phosphatidylserine Exposure and Microvesicle Release from Human Purified Platelets
Published on: November 29, 2024
Phospholipid-esterified eicosanoids are generated in agonist-activated human platelets and enhance tissue
Christopher P Thomas1, Lloyd T Morgan, Benjamin H Maskrey
1Department of Infection, Cardiff University, Cardiff CF14 4XN, United Kingdom.
The Journal of Biological Chemistry
|January 12, 2010
Summary
Novel lipids, phosphatidylethanolamine (PE)- or phosphatidylcholine (PC)-esterified 12S-hydroxyeicosatetraenoic acid (12S-HETE), were identified. These esterified HETEs promote coagulation and are formed via receptor mechanisms, not just disease.
Area of Science:
- Biochemistry
- Lipidomics
- Molecular Biology
Background:
- 12-lipoxygenase generates 12S-hydroxyeicosatetraenoic acid (12S-HETE), a bioactive lipid mediator.
- Oxidized phospholipids are implicated in vascular and inflammatory diseases.
- The formation pathways and functions of esterified HETEs remain largely uncharacterized.
Purpose of the Study:
- To identify and characterize specific PE- or PC-esterified 12S-HETE lipids.
- To elucidate the mechanisms of their formation and cellular localization.
- To investigate their role in platelet function and coagulation.
Main Methods:
- Lipidomic analysis of activated platelets.
- Stable isotope labeling to track lipid formation.
- Biochemical assays to assess signaling pathways.
- Functional studies using platelets from Scott syndrome patients and liposomes.
Main Results:
- PE- or PC-esterified 12S-HETE lipids were identified and rapidly formed upon platelet activation.
- Their generation is stimulated by protease-activated receptors and involves Ca(2+) mobilization and various signaling enzymes.
- Esterified HETEs remain cell-associated, with HETE-PEs externalized to the plasma membrane.
- Inhibition of 12-lipoxygenase reduced HETE-PE externalization.
- Defective HETE-PE externalization was observed in Scott syndrome platelets.
- HETE-PC enhanced thrombin generation in vitro, suggesting a procoagulant role.
Conclusions:
- Novel esterified HETEs (12S-HETE-PE/PCs) are formed via receptor-mediated mechanisms.
- These lipids play a role in platelet externalization and promote coagulation.
- Their formation is distinct from passive oxidation and suggests active biological roles in hemostasis.
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