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Title: Observational study of inflammatory profiles in patients with ST-elevation myocardial infarction stratified by plaque erosion or rupture identified by optical coherence tomography : the Plaque Erosion Pilot Study
Author: Chandran, Sujay
ISNI:       0000 0004 7426 9416
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2017
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Background: Plaque erosion is responsible for 30–40% of ST-elevation myocardial infarction (STEMI) cases, but the underlying cause is unknown. Autopsy studies suggest that inflammatory infiltrates are less abundant in erosion compared to plaque rupture, which suggests that other pathological mechanisms are important. So far, different inflammatory profiles have not been demonstrated in vivo. Objectives: We sought to characterise the inflammatory profiles of plaque rupture and plaque erosion in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). Methods: Forty STEMI patients undergoing PPCI with less than six hours of chest pain were recruited in a single-centre observational study. Blood samples were taken from the infarct-related artery and a peripheral artery. Culprit plaques were imaged using optical coherence tomography (OCT) before PCI and classified by three blinded observers as ruptured fibrous cap (RFC) or intact fibrous cap (IFC). The expression profiles of 102 cytokines were measured using an array, and comparisons of the two pathological groups were performed using the Significance Analysis of Microarrays (SAM) methodology. Significant cytokines were validated with enzyme-linked immunosorbent assay (ELISA) and this was confirmed statistically using Wilcoxon rank-sum tests. Thrombectomy samples were analysed for differential mRNA expression using real-time polymerase chain reaction (RT-PCR). Results: Twenty-three lesions were classified as RFC (58%), fifteen as IFC (38%) and two were undefined (4%). Overall, 12% (12/102) of cytokines were differentially expressed in both coronary and peripheral plasma. We selected the most significant differences and confirmed that IFC was associated with preferential expression of epidermal growth factor (EGF) (coronary samples: SAM adjusted P < 0.001; ELISA IFC 7.42 vs RFC 6.63 log2 pg/ml, P = 0.036) and Thrombospondin-1 (TSP-1) (coronary samples: SAM adjusted P = 0.03; ELISA IFC 10.4 vs RFC 8.65 log2 ng/ml, P = 0.0041). Interferon-inducible T-cell alpha chemoattractant (I-TAC) was preferentially expressed in RFC (coronary samples: SAM adjusted P < 0.001; ELISA IFC 10.2 vs RFC 10.8 log2 pg/ml; P = 0.042). Thrombectomy mRNA demonstrated significantly elevated EGF expression in IFC (P = 0.0264) and I-TAC in RFC (P = 0.0007), but no differences in expression of TSP-1. Conclusions: Distinct inflammatory profiles for RFC and IFC are demonstrable in coronary plasma and thrombectomy specimens in STEMI patients. IFC is associated with elevated intracoronary EGF and TSP-1. These results may help to further understand the pathophysiology of plaque erosion and to potentially tailor future treatment strategies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available