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The use of microparticles and inflammatory cytokines as potential biomarkers for plaque instability in patients with carotid disease

Schiro, Andrew

[Thesis]. Manchester, UK: The University of Manchester; 2015.

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Abstract

AbstractAim: Endothelial microparticles (EMPs) are released from dysfunctional endothe-lial 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 inflamma-tory and bone-related proteins. Immunohistological analysis detailed the contribu-tion of differentially-regulated systemic markers to plaque pathology. Alizarin red staining showed calcification. Results: EMPs were significantly higher in patients with carotid stenosis (≥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.

Bibliographic metadata

Type of resource:
Content type:
Form of thesis:
Type of submission:
Degree type:
Doctor of Medicine
Degree programme:
MD Medicine (Cardiovascular Sciences)
Publication date:
Location:
Manchester, UK
Total pages:
202
Abstract:
AbstractAim: Endothelial microparticles (EMPs) are released from dysfunctional endothe-lial 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 inflamma-tory and bone-related proteins. Immunohistological analysis detailed the contribu-tion of differentially-regulated systemic markers to plaque pathology. Alizarin red staining showed calcification. Results: EMPs were significantly higher in patients with carotid stenosis (≥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.
Thesis main supervisor(s):
Language:
en

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:280242
Created by:
Schiro, Andrew
Created:
27th November, 2015, 13:45:06
Last modified by:
Schiro, Andrew
Last modified:
9th January, 2019, 09:49:45

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