Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers

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dc.check.embargoformatBoth hard copy thesis and e-thesisen
dc.check.opt-outNot applicableen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorDinan, Timothy G.en
dc.contributor.authorDollard, James
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2016-06-01T10:26:36Z
dc.date.issued2016
dc.date.submitted2016
dc.description.abstractCardiac Syndrome X (CSX), the presence of angina pectoris with objective signs of myocardial ischaemia despite angiographically normal epicardial coronary arteries, appears to be due to coronary microvascular dysfunction and is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We aimed to further characterise this relationship by prospectively analysing a wide variety of molecular biomarkers in a cohort of CSX patients thereby charting the changes in biomarkers throughout the natural history of CSX from its initial diagnosis to eventual disease quiescence. We found that CSX patients, when compared to healthy controls, have a persistent low-grade systemic inflammatory response characterised by an elevation of Tumour Necrosis Factor and Interferon-gamma, regardless of the presence of contemporaneous signs or symptoms of disease activity. Interleukin-6 and C-reactive Protein (CRP) are only elevated when patients have clinical evidence of disease activity and may be state markers in CSX. Moreover, CRP levels appear to correlate with signals of disease severity such as the time taken to develop symptoms during exercise stress testing. We have also demonstrated that the enzyme Indoleamine-2,3- dioxygenase is upregulated in active disease thus providing a possible explanation for the increased burden of psychological disease encountered in CSX. Analysis of the microRNA transcriptome showed that miR-143 is significantly under-expressed in CSX patients. This could allow phenotype switching in vascular smooth muscle cells with the resultant vascular remodelling causing reduced vessel responsiveness to local rheological stimuli and reduced luminal diameter with consequent increased microvascular resistance during times of increased myocardial oxygen demand, thereby limiting maximal hyperaemia during exercise. Our findings corroborate many previous hypotheses regarding the role of inflammation in CSX, generate new insights into possible pathogenic mechanisms and offer new therapeutic targets for the future management of this important cardiological condition.en
dc.description.sponsorshipHealth Research Board (HPF-2011-22)en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDollard, J. 2016. Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers. PhD Thesis, University College Cork.en
dc.identifier.endpage381en
dc.identifier.urihttps://hdl.handle.net/10468/2661
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2016, James Dollard.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectCardiologyen
dc.subjectBiomarkeren
dc.subjectInflammationen
dc.subjectEpidemiologyen
dc.subjectTryptophanen
dc.subjectCytokineen
dc.subjectCardiovascularen
dc.subjectAngina pectorisen
dc.subjectMicroRNAen
dc.subjectMicrovascular anginaen
dc.subjectCardiac syndrome xen
dc.thesis.opt-outfalse
dc.titleAssessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkersen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Medicine and Health)en
ucc.workflow.supervisort.dinan@ucc.ie
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