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Title: A genomic and proteomic study to investigate the phenomenon of aspirin resistance
Author: York, E. A.
ISNI:       0000 0004 2726 4524
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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Platelets are anucleate fragments of megakaryocytes and have a central role in haemostasis responding to a variety of agents and stimuli initiating a series of events ending in activation and aggregation. At unstable plaques platelets can initiate atherothrombosis leading to complete occlusion of the vessel. Aspirin is a nonsteroidal anti-inflammatory drug and has been shown to reduce the risk of myocardial infarction and stroke in susceptible patients by approximately 25%. However, some patients, despite aspirin therapy, experience further vascular events suggesting that they aspirin 'resistant'. Clinical aspirin resistance refers to patients who, despite compliance with a therapeutic dose (?75 mg), continue to experience recurrent thrombotic events; biochemical aspirin resistance uses laboratory methods to indicate the failure of aspirin to inhibit platelet activity. In this study the human megakaryoblastic cell line (MEG-Ol) was used as a model, which exhibits both phenotypic and biochemical properties observed in pro-platelet megakaryopoiesis. In this study Meg-Ol cells were exposed to clinically relevant concentrations of aspirin and salicylate to observe the resultant global and sub- proteomes. As platelets are anucleate, proteornic techniques can investigate changes -\ .-i - •. in protein expression associated with aspirin resistance. This study also examined protein expression changes in response to therapeutic doses of aspirin in the global and sub-proteornes of platelets isolated from a healthy volunteer population classified as ASA·sensitive or AS A-resistant based on the PFA-lOO platelet functionality test. The findings of the present study show that the expression of important proteins in the well characterised megakaryocyte cell line, Meg-Ol , are modified following' exposure to both aspirin and salicylate. In addition the proteomes of platelets isolated from AS A-resistant and ASA-sensitive individuals differ in the expression of proteins. This study has shown that aspirin and salicylate treatment can alter the expression of numerous proteins independently of COX, which were directly or indirectly involved in platelet activation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available