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Both hard copy thesis and e-thesis Not applicable This thesis is due for publication or the author is actively seeking to publish this material Dinan, Timothy G. Dollard, James Health Research Board 2016-06-01T10:26:36Z 2016 2016 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. Health Research Board (HPF-2011-22) Not peer reviewed Accepted Version application/pdf Dollard, J. 2016. Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers. PhD Thesis, University College Cork. 381 https://hdl.handle.net/10468/2661 en University College Cork © 2016, James Dollard. http://creativecommons.org/licenses/by-nc-nd/3.0/ Cardiology Biomarker Inflammation Epidemiology Tryptophan Cytokine Cardiovascular Angina pectoris MicroRNA Microvascular angina Cardiac syndrome x false Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers Doctoral thesis Doctoral PhD (Medicine and Health) t.dinan@ucc.ieinfo:eu-repo/semantics/openAccess