title: Elevated levels of endothelial-derived microparticles, and serum CXCL9 and SCGF-β are associated with unstable asymptomatic carotid plaques.
abstract: 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 may correlate with serum markers of plaque instability and inflammation. Circulating EMPs, platelet MPs (PMPs) and inflammatory markers were measured in healthy controls and patients undergoing carotid endarterectomy. EMP/PMPs 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. EMPs and PMPs 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, CXCL9 and SCGF-β compared to those with stable plaques. CXCL9, 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. These data could be important in identifying patients at most benefit from intervention.
authors.affiliation: Regional Vascular and Endovascular Unit, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester, UK, M13 9WL.|Institute of Cardiovascular Science, Manchester Academic Health Science Centre, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester, UK, M13 9NT.
authors.forename: Andrew
authors.initials: A
authors.lastname: Schiro
authors.affiliation: Translational Science, Healthcare Science Research Institute, Faculty of Science and Engineering, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester, UK, M1 5GD.
authors.forename: Fiona L
authors.initials: FL
authors.lastname: Wilkinson
authors.affiliation: Translational Science, Healthcare Science Research Institute, Faculty of Science and Engineering, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester, UK, M1 5GD.
authors.forename: Ria
authors.initials: R
authors.lastname: Weston
authors.affiliation: Regional Vascular and Endovascular Unit, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester, UK, M13 9WL.
authors.forename: J Vincent
authors.initials: JV
authors.lastname: Smyth
authors.affiliation: Regional Vascular and Endovascular Unit, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester, UK, M13 9WL.|Institute of Cardiovascular Science, Manchester Academic Health Science Centre, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester, UK, M13 9NT.|Translational Science, Healthcare Science Research Institute, Faculty of Science and Engineering, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester, UK, M1 5GD.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Serracino-Inglott
authors.affiliation: Institute of Cardiovascular Science, Manchester Academic Health Science Centre, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester, UK, M13 9NT.|Translational Science, Healthcare Science Research Institute, Faculty of Science and Engineering, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester, UK, M1 5GD.
authors.forename: M Yvonne
authors.initials: MY
authors.lastname: Alexander
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016893:Carotid Stenosis / Q000097:blood / Q000378:metabolism / Q000601:surgery*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000097:blood*; D016207:Cytokines / Q000097:blood; D016894:Endarterectomy, Carotid; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D037181:Lectins, C-Type / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D053495:Osteopontin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood
chemical_list: C110532:CLEC11A protein, human; D054370:Chemokine CXCL9; D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D053244:Osteoprotegerin; D015675:Osteocalcin; D053495:Osteopontin