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Title: The use of microparticles and inflammatory cytokines as potential biomarkers for plaque instability in patients with carotid disease
Author: Schiro, Andrew
ISNI:       0000 0004 7655 6291
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2015
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Aim: Endothelial microparticles (EMPs) are released from dysfunctional endothelial cells. We hypothesised that patients with unstable carotid plaque have higher levels of circulating microparticles compared to patients with stable plaques, and this may correlate with serum markers of plaque instability and inflammation. Method: Circulating EMPs and inflammatory markers were measured in twenty healthy controls and seventy patients undergoing carotid endarterectomy. EMPs were quantified using flow cytometry. Bioplex assays profiled systemic inflammatory and bone-related proteins. Immunohistological analysis detailed the contribution of differentially-regulated systemic markers to plaque pathology. Alizarin red staining showed calcification. Results: EMPs were significantly higher in patients with carotid stenosis (greater than or equal to 70%) compared to controls, with no differences between asymptomatic vs symptomatic patients. Asymptomatic patients with unstable plaques exhibited higher levels of EMPs compared to those with stable plaques, with a similar trend observed in symptomatic patients. CXCL9 and SCGF-β were significantly elevated in asymptomatic patients with unstable plaques, with IL-16 and macrophage inhibitory factor significantly elevated in the stable plaque group. CXCL9, CTACK and SCGF-β were detected within all plaques, suggesting a contribution to both localised and systemic inflammation. Osteopontin and osteoprotegerin were significantly elevated in the symptomatic vs asymptomatic group, while osteocalcin was higher in asymptomatic patients with stable plaque. All plaques exhibited calcification, which was significantly greater in asymptomatic patients. This may impact on plaque stability. Conclusions: Circulatory EMP, CXCL9 and SCGF-β levels are raised in asymp-tomatic patients with unstable plaques, which could be important in identifying patients at most benefit from intervention.
Supervisor: Boulton, Andrew Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Stroke ; endothelial microparticles ; cytokines