Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.674998
Title: The role of thrombin activatable fibrinolysis inhibitor in abdominal aortic aneurysms
Author: Bridge, Katherine Isabella
ISNI:       0000 0004 5370 4087
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2015
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Abstract:
Thrombin-activatable fibrinolysis inhibitor (TAFI) prevents the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Patients with abdominal aortic aneurysms (AAA), in common with a number of cardiovascular diseases, display an altered fibrin clot structure, with denser clots that have smaller pores and an increased resistance to lysis. Murine studies have implicated a potential role for TAFI in AAA disease. This study aimed to investigate the role of TAFI in human AAA, and to complement this with an investigation into the effect of TAFI inhibition on AAA development and progression in-vivo. By measuring the plasma levels of TAFI zymogen, activated and inactivated TAFI, and the TAFI activation peptide in plasma samples, and using clot lysis assays to determine in-vitro TAFI activity, this study indicated increased turnover of TAFI in patients with AAA. Further to this, it was determined that the delay in lysis previously demonstrated in patients with AAA could be corrected through the inhibition of TAFI. Inhibition of TAFI in-vivo resulted in a decrease in mortality in the Angiotensin II model of AAA. The site of action of the inhibitor determined the effect on AAA formation, however, with inhibition of plasmin-mediated TAFI activation resulting in a decrease in AAA formation rates, whilst inhibition of all active TAFI resulted in an increase in AAA formation rates. Delayed TAFI inhibition following the formation of AAA had no effect on AAA progression. This study demonstrated evidence of increased TAFI turnover in patients with AAA, whilst in-vivo studies indicate a role for TAFI early in the development of AAA disease.
Supervisor: Ariëns, Robert ; Scott, Julian Sponsor: British Heart Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.674998  DOI: Not available
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