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dc.contributor.advisorPreston, Roger
dc.contributor.authorNí Áinle, Fionnuala Bríd
dc.date.accessioned2017-02-08T11:54:18Z
dc.date.available2017-02-08T11:54:18Z
dc.date.issued2011
dc.identifier.citationFionnuala Bríd Ní Áinle, 'Modulation of activated protein C (APC) anticoagulant and cytoprotective function', [thesis], Trinity College (Dublin, Ireland). School of Medicine. Discipline of Haematology, 2011, pp 291
dc.identifier.otherTHESIS 9694
dc.identifier.urihttp://hdl.handle.net/2262/79271
dc.description.abstractActivated protein C (APC) is an anticoagulant glycoprotein that attenuates thrombin generation. Moreover, it has recently been demonstrated that APC possesses anti-inflammatory, anti-apoptotic and endothelial cell barrier stabilizing properties. The first goal of this thesis was to study the role of N-linked carbohydrates (glycans) in modulating APC anticoagulant function and endothelial cytoprotective signalling via the endothelial cell protein C receptor (EPCR) and protease activated receptor 1 (PAR1). It was determined that removal of APC N-linked glycans using the enzyme PNGase resulted in a ~6-fold reduction in the APC concentration required to achieve half-maximal inhibition of thrombin-induced endothelial cell barrier permeability. Furthermore, deglycosylation enhanced APC anti-apoptotic function on endothelial cells compared to untreated APC. Recombinant APC variants were generated in which each Asn-linked glycan attachment site was eliminated by amino acid substitution. The variant APC-N329Q displayed up to 5-fold enhanced protection of the endothelial barrier compared to wild type APC. Moreover, an APC variant (APC-L38D/N329Q) was generated which possessed minimal anticoagulant activity but 5-fold improved endothelial barrier protective function compared to wild type APC.
dc.format1 volume
dc.language.isoen
dc.publisherTrinity College (Dublin, Ireland). School of Medicine. Discipline of Haematology
dc.relation.isversionofhttp://stella.catalogue.tcd.ie/iii/encore/record/C__Rb15151787
dc.subjectHaemostasis Research Group, Ph.D.
dc.subjectPh.D. Trinity College Dublin
dc.titleModulation of activated protein C (APC) anticoagulant and cytoprotective function
dc.typethesis
dc.type.supercollectionthesis_dissertations
dc.type.supercollectionrefereed_publications
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (Ph.D.)
dc.rights.ecaccessrightsopenAccess
dc.format.extentpaginationpp 291
dc.description.noteTARA (Trinity’s Access to Research Archive) has a robust takedown policy. Please contact us if you have any concerns: rssadmin@tcd.ie


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