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

Autor:	Hajeyah AA; Systems Immunity Research Institute and Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom; Department of Biological Sciences, Kuwait University, Safat, Kuwait. Electronic address: ali.hajeyah@ku.edu.kw., Protty MB; Systems Immunity Research Institute and Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom., Paul D; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA., Costa D; Systems Immunity Research Institute and Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom., Omidvar N; Systems Immunity Research Institute and Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom., Morgan B; Systems Immunity Research Institute and Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom., Iwasaki Y; College of Bioscience and Biotechnology, Chubu University, Kasugai, Japan., McGill B; Systems Immunity Research Institute and Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom., Jenkins PV; University Hospital of Wales, Cardiff, United Kingdom., Yousef Z; University Hospital of Wales, Cardiff, United Kingdom., Allen-Redpath K; Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom., Soyama S; Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom., Choudhury A; Morriston Cardiac Centre, Swansea, United Kingdom., Mitra R; University Hospital of Wales, Cardiff, United Kingdom., Yaqoob P; Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom., Morrissey JH; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA., Collins PW; Systems Immunity Research Institute and Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom; University Hospital of Wales, Cardiff, United Kingdom., O'Donnell VB; Systems Immunity Research Institute and Division of Infection and Immunity, Cardiff University, Cardiff, United Kingdom. Electronic address: o-donnellvb@cardiff.ac.uk.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Jan; Vol. 65 (1), pp. 100484. Date of Electronic Publication: 2023 Dec 14.
DOI:	10.1016/j.jlr.2023.100484
Abstrakt:	Aminophospholipids (aPL) such as phosphatidylserine are essential for supporting the activity of coagulation factors, circulating platelets, and blood cells. Phosphatidylthreonine (PT) is an aminophospholipid 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, and isolated leukocytes from healthy volunteers using liquid chromatography-tandem mass spectrometry. 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 phosphatidylserine. 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 extracellular vesicle 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 procoagulant membrane, and may support thrombosis in patients at elevated risk. Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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