Academic Journal
Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease.
| العنوان: | Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease. |
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| المؤلفون: | Hajeyah, Ali A., Protty, Majd B., Paul, Divyani, Costa, Daniela, Omidvar, Nader, Morgan, Bethan, Iwasaki, Yugo, McGill, Beth, Jenkins, P. Vincent, Yousef, Zaheer, Allen-Redpath, Keith, Soyama, Shin, Choudhury, Anirban, Mitra, Rito, Yaqoob, Parveen, Morrissey, James H., Collins, Peter W., O'Donnell, Valerie B. |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2024 |
| المجموعة: | Cardiff University: ORCA (Online Research @ Cardiff) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://orca.cardiff.ac.uk/id/eprint/165179/1/PIIS0022227523001578.pdf; Hajeyah, Ali A., Protty, Majd B. https://orca.cardiff.ac.uk/view/cardiffauthors/A1427892W.html, Paul, Divyani, Costa, Daniela https://orca.cardiff.ac.uk/view/cardiffauthors/A2482427P.html orcid:0000-0001-8821-5898 orcid:0000-0001-8821-5898, Omidvar, Nader https://orca.cardiff.ac.uk/view/cardiffauthors/A039332V.html, Morgan, Bethan https://orca.cardiff.ac.uk/view/cardiffauthors/A2643101I.html, Iwasaki, Yugo, McGill, Beth, Jenkins, P. Vincent, Yousef, Zaheer, Allen-Redpath, Keith, Soyama, Shin, Choudhury, Anirban, Mitra, Rito, Yaqoob, Parveen, Morrissey, James H., Collins, Peter W. https://orca.cardiff.ac.uk/view/cardiffauthors/A070283V.html orcid:0000-0002-6410-1324 orcid:0000-0002-6410-1324 and O'Donnell, Valerie B. https://orca.cardiff.ac.uk/view/cardiffauthors/A054395H.html orcid:0000-0003-4089-8460 orcid:0000-0003-4089-8460 2024. Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease. Journal of Lipid Research 65 (1) , 100484. 10.1016/j.jlr.2023.100484 https://doi.org/10.1016/j.jlr.2023.100484 file https://orca.cardiff.ac.uk/id/eprint/165179/1/PIIS0022227523001578.pdf |
| DOI: | 10.1016/j.jlr.2023.100484 |
| الاتاحة: | https://orca.cardiff.ac.uk/id/eprint/165179/ https://doi.org/10.1016/j.jlr.2023.100484 https://orca.cardiff.ac.uk/id/eprint/165179/1/PIIS0022227523001578.pdf |
| Rights: | cc_by_4_0 |
| رقم الانضمام: | edsbas.3BAD8FEC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jlr.2023.100484 |
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