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

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dc.contributor.advisor Dinan, Timothy G. en Dollard, James 2016-06-01T10:26:36Z 2016 2016
dc.identifier.citation Dollard, J. 2016. Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers. PhD Thesis, University College Cork. en
dc.identifier.endpage 381 en
dc.description.abstract Cardiac 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.sponsorship Health Research Board (HPF-2011-22) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2016, James Dollard. en
dc.rights.uri en
dc.subject Cardiology en
dc.subject Biomarker en
dc.subject Inflammation en
dc.subject Epidemiology en
dc.subject Tryptophan en
dc.subject Cytokine en
dc.subject Cardiovascular en
dc.subject Angina pectoris en
dc.subject MicroRNA en
dc.subject Microvascular angina en
dc.subject Cardiac syndrome x en
dc.title Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text available en
dc.description.version Accepted Version
dc.contributor.funder Health Research Board en
dc.description.status Not peer reviewed en Medicine en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Both hard copy thesis and e-thesis en
dc.internal.conferring Summer 2016 en

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© 2016, James Dollard. Except where otherwise noted, this item's license is described as © 2016, James Dollard.
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