Characterisation of phosphatidylthreonine in human blood

Hajeyah, Ali 2022. Characterisation of phosphatidylthreonine in human blood. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Phosphatidylthreonine (PT) is an anionic phospholipid that was previously reported in animal tissues, cell cultures, bacteria, and protozoa, but not human tissues. PT is a structural analogue of phosphatidylserine (PS), a phospholipid with a recognised role in blood coagulation. This thesis investigates the occurrence of PT in human blood and its potential roles in blood coagulation and coronary artery disease. Using liquid chromatography–tandem mass spectrometry (LC-MS/MS), I demonstrated the presence of PT in human blood, platelets, extracellular vesicles (EV), and leukocytes. PT was enriched in the inner membrane leaflet of resting platelets but was externalised into the outer leaflet in response to thrombin activation. Additionally, total platelet PT decreased in response to thrombin activation. These findings suggest roles for PT in platelet activation and aggregation. Next, I investigated the ability of PT to support coagulation in vitro using coagulation assays. PT supported coagulation through enhancement of prothrombinase activity but not extrinsic tenase activity. This suggests that PT functions in the propagation but not initiation of coagulation, contrasting with PS which functions in both processes. Last, I measured PT in platelets, EVs, and leukocytes from a clinical cohort of coronary artery disease. PT was significantly higher in platelets and EVs from the disease groups compared to healthy volunteers, suggesting a link between PT and coronary artery disease. In summary, PT is a native lipid in human blood cells, possesses procoagulant properties in vitro, and its levels are significantly higher in platelets and EVs from coronary artery disease patients compared to healthy volunteers. However, many aspects of PT’s biochemistry are unknown, including its metabolism, functions in vivo, and involvement in vascular disease.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	14 December 2022
Last Modified:	06 Jan 2024 04:38
URI:	https://orca.cardiff.ac.uk/id/eprint/154935

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