Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease

Hajeyah, A. A., Protty, M. B., Paul, D., Costa, D., Omidvar, N., Morgan, B., Iwasaki, Y., McGill, B., Jenkins, P. V., Yousef, Z., Allen-Redpath, K., Soyama, S., Choudhury, A., Mitra, R., Yaqoob, P. ORCID: https://orcid.org/0000-0002-6716-7599, Morrissey, J. H., Collins, P. W. and O'Donnell, V. B. (2023) Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease. Journal of Lipid Research. 100484. ISSN 1539-7262 doi: 10.1016/j.jlr.2023.100484

Abstract/Summary

Aminophospholipids (aPL) such as phosphatidylserine (PS) are essential for supporting the activity of coagulation factors, circulating platelets and blood cells. Phosphatidylthreonine (PT) is an aPL previously reported in eukaryotic parasites and animal cell cultures, but not yet in human tissues. Here, we evaluated whether PT is present in blood cells and characterized its ability to support coagulation. Several PT molecular species were detected in human blood, washed platelets, extracellular vesicles (EV), and isolated leukocytes from healthy volunteers using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The ability of PT to support coagulation was demonstrated in vitro using biochemical and biophysical assays. In liposomes, PT supported prothrombinase activity in the presence and absence of PS. PT nanodiscs strongly bound FVa and lactadherin (nM affinity), but poorly bound prothrombin and FX, suggesting that PT supports prothrombinase through recruitment of FVa. PT liposomes bearing tissue factor poorly generated thrombin in platelet poor plasma, indicating that PT poorly supports extrinsic tenase activity. On platelet activation, PT is externalized and partially metabolized. Last, PT was significantly higher in platelets and EV from patients with coronary artery disease, than in healthy controls. In summary, PT is present in human blood, binds FVa and lactadherin, supports coagulation in vitro through FVa binding, and is elevated in atherosclerotic vascular disease. Our studies reveal a new phospholipid subclass, that contributes to the pro-coagulant membrane, and may support thrombosis in patients at elevated risk.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/114416
Identification Number/DOI	10.1016/j.jlr.2023.100484
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
Publisher	American Society for Biochemistry and Molecular Biology
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