Please use this identifier to cite or link to this item:
http://bura.brunel.ac.uk/handle/2438/29132
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Hajeyah, AA | - |
dc.contributor.author | Protty, MB | - |
dc.contributor.author | Paul, D | - |
dc.contributor.author | Costa, D | - |
dc.contributor.author | Omidvar, N | - |
dc.contributor.author | Morgan, B | - |
dc.contributor.author | Iwasaki, Y | - |
dc.contributor.author | McGill, B | - |
dc.contributor.author | Jenkins, PV | - |
dc.contributor.author | Yousef, Z | - |
dc.contributor.author | Allen-Redpath, K | - |
dc.contributor.author | Soyama, S | - |
dc.contributor.author | Choudhury, A | - |
dc.contributor.author | Mitra, R | - |
dc.contributor.author | Yaqoob, P | - |
dc.contributor.author | Morrissey, JH | - |
dc.contributor.author | Collins, PW | - |
dc.contributor.author | O'Donnell, VB | - |
dc.date.accessioned | 2024-06-06T13:13:05Z | - |
dc.date.available | 2024-06-06T13:13:05Z | - |
dc.date.issued | 2024-01-04 | - |
dc.identifier | ORCiD: Divyani Paul https://orcid.org/0000-0002-4544-1825 | - |
dc.identifier | ORCiD: Yugo Iwasaki https://orcid.org/0000-0003-2784-9269 | - |
dc.identifier | ORCiD: Beth McGill https://orcid.org/0000-0001-5714-453X | - |
dc.identifier | ORCiD: Keith Allen-Redpath https://orcid.org/0009-0004-7213-2675 | - |
dc.identifier | ORCiD: Rito Mitra https://orcid.org/0000-0001-6031-8385 | - |
dc.identifier | ORCiD: Parveen Yaqoob https://orcid.org/0000-0002-6716-7599 | - |
dc.identifier | ORCiD: James H. Morrissey https://orcid.org/0000-0002-1570-1569 | - |
dc.identifier.citation | Hajeyah, A.A. et al. (2024) 'Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease', Journal of Lipid Research, 65 (1), pp. 1 - 15. doi: 10.1016/j.jlr.2023.100484. | en_US |
dc.identifier.issn | 0022-2275 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/29132 | - |
dc.description | Data availability: All data produced in the present study are available upon reasonable request to the authors (contact Ali A. Hajeyah, ali.hajeyah@ku.edu.kw). | en_US |
dc.description | Supplemental Data are available online at: https://www.sciencedirect.com/science/article/pii/S0022227523001578?via%3Dihub#sec5 and https://www.sciencedirect.com/science/article/pii/S0022227523001578?via%3Dihub#appsec1 . | - |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | A. A. H. acknowledges funding from Kuwait University and support from Kuwait Cultural Office (KCO) in London. M. B. P. was funded by the Wellcome Trust (GW4-CAT fellowship 216278/Z/19/Z) and Academy of Medical Sciences Starter Grant (SGL026∖1037). D. C., P. W. C., and V. B. O. D. acknowledge funding from British Heart Foundation (Programme Grant RG/F/20/110020). Funding from EU Marie Sklodowska-Curie ITN ArthritisHeal is acknowledged (V. B. O. D., D. C.). D. P. and J. H. M. acknowledge support from the NIH Common Fund (Grant R01 GM123455) and the National Heart, Lung, and Blood Institute of NIH (Grant R35 HL135823). | en_US |
dc.format.medium | Print-Electronic | - |
dc.language.iso | en_US | en_US |
dc.publisher | Elsevier on behalf of American Society for Biochemistry and Molecular Biology | en_US |
dc.rights | Copyright © 2023 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/). | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | phospholipids | en_US |
dc.subject | phospholipids/metabolism | en_US |
dc.subject | phospholipids/biosynthesis | en_US |
dc.subject | vascular biology | en_US |
dc.subject | platelets | en_US |
dc.subject | phosphatidylthreonine | en_US |
dc.subject | blood coagulation | en_US |
dc.subject | coronary artery disease | en_US |
dc.title | Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease | en_US |
dc.type | Article | en_US |
dc.date.dateAccepted | 2023-12-14 | - |
dc.identifier.doi | https://doi.org/10.1016/j.jlr.2023.100484 | - |
dc.relation.isPartOf | Journal of Lipid Research | - |
pubs.issue | 1 | - |
pubs.publication-status | Published | - |
pubs.volume | 65 | - |
dc.identifier.eissn | 1539-7262 | - |
dc.rights.license | https://creativecommons.org/licenses/by/4.0/legalcode.en | - |
dc.rights.holder | The Authors | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
FullText.pdf | Copyright © 2023 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/). | 2.55 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License