Majumder, B; (2012) An investigation into the role of platelet- monocyte interaction and inflammation in coronary artery disease. Doctoral thesis , UCL (University College London).

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Abstract

Introduction: - Platelet monocyte complex (PMC) formation has been widely reported as a marker of platelet activation in vascular disease states and several studies have shown heightened systemic expression of PMC in stable and acute coronary disease. However, the relationship between intracoronary platelet and monocyte activation status and local intracoronary inflammation in acute coronary syndrome (ACS) remains unclear. Method:- Fifteen ST elevation myocardial infarction (STEMI), 8 non ST elevation myocardial infarction (NSTEMI) and 7 stable angina patients were recruited. PMC, P selectin positive PMC (activated platelet within the complex), tissue factor (TF) positive PMC (activated monocyte within the complex) were estimated with flow cytometry from blood samples aspirated from the coronary artery (distal to the lesion), aorta and right atrium . Plasma CRP, SAA, TNF –alpha and IL-6 were also measured. Results:- In ACS patients no significant transculprit lesion gradient of PMC expression was observed but significant gradients were found with P-selectin positive PMC (p= 0.01) and TF positive PMC expression (p=0.04). Overall median P- selectin positive PMC expression in ACS patients was significantly higher compared to stable angina (p= 0.006). Intracoronary P-selectin positive PMC was also found to be higher in the ACS group compared to stable group (p=0.003). Overall median CRP (p= 0.001), SAA (p=0.0007) and IL-6 (p= 0.03) levels were significantly higher in ACS. In STEMI intracoronary PMC correlated positively with intracoronary TNF-alpha (r= 0.68, p= 0.03). Positive correlation was also observed between intracoronary TF positive PMC (% monocyte) with TNF-alpha and IL-6 (r=0.66, p=0.05 & r=0.71, p= 0.05 respectively). Conclusion:- The work outlined in this thesis has demonstrated the importance of platelet and monocyte activation status of the PMC as a determinant of intracoronary inflammation. Beyond a local intracoronary role, PMC may contribute to systemic inflammation through P-selectin expression and local intracoronary inflammation through increased P-selectin and tissue factor expression.

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