title: Predicting carotid artery disease and plaque instability from cell-derived microparticles.
abstract: OBJECTIVE
  Cell-derived microparticles (MPs) are small plasma membrane-derived vesicles shed from circulating blood cells and may act as novel biomarkers of vascular disease. We investigated the potential of circulating MPs to predict (a) carotid plaque instability and (b) the presence of advanced carotid disease.
  
  
  METHODS
  This pilot study recruited carotid disease patients (aged 69.3 ± 1.2 years [mean ± SD], 69% male, 90% symptomatic) undergoing endarterectomy (n = 42) and age- and sex-matched controls (n = 73). Plaques were classified as stable (n = 25) or unstable (n = 16) post surgery using immunohistochemistry. Blood samples were analysed for MP subsets and molecular biomarkers. Odds ratios (OR) are expressed per standard deviation biomarker increase.
  
  
  RESULTS
  Endothelial MP (EMP) subsets, but not any vascular, inflammatory, or proteolytic molecular biomarker, were higher (p < .05) in the unstable than the stable plaque patients. The area under the receiver operator characteristic curve for CD31(+)41(-) EMP in discriminating an unstable plaque was 0.73 (0.56-0.90, p < .05). CD31(+)41(-) EMP predicted plaque instability (OR = 2.19, 1.08-4.46, p < .05) and remained significant in a multivariable model that included transient ischaemic attack symptom status. Annexin V(+) MP, platelet MP (PMP) subsets, and C-reactive protein were higher (p < .05) in cases than controls. Annexin V(+) MP (OR = 3.15, 1.49-6.68), soluble vascular cell adhesion molecule-1 (OR = 1.64, 1.03-2.59), and previous smoking history (OR = 3.82, 1.38-10.60) independently (p < .05) predicted the presence of carotid disease in a multivariable model.
  
  
  CONCLUSIONS
  EMP may have utility in predicting plaque instability in carotid patients and annexin V(+) MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers.
authors.affiliation: Biomedical Research Group, Schools of Health Science and Science, Waterford Institute of Technology, Waterford, Ireland.
authors.forename: A L
authors.initials: AL
authors.lastname: Wekesa
authors.affiliation: Departments of Vascular Surgery and Histopathology, Waterford Regional Hospital, Waterford, Ireland; Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: K S
authors.initials: KS
authors.lastname: Cross
authors.affiliation: Biomedical Research Group, Schools of Health Science and Science, Waterford Institute of Technology, Waterford, Ireland.
authors.forename: O
authors.initials: O
authors.lastname: O'Donovan
authors.affiliation: Departments of Vascular Surgery and Histopathology, Waterford Regional Hospital, Waterford, Ireland.
authors.forename: J F
authors.initials: JF
authors.lastname: Dowdall
authors.affiliation: Departments of Vascular Surgery and Histopathology, Waterford Regional Hospital, Waterford, Ireland.
authors.forename: O
authors.initials: O
authors.lastname: O'Brien
authors.affiliation: Departments of Vascular Surgery and Histopathology, Waterford Regional Hospital, Waterford, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Doyle
authors.affiliation: Departments of Vascular Surgery and Histopathology, Waterford Regional Hospital, Waterford, Ireland.
authors.forename: L
authors.initials: L
authors.lastname: Byrne
authors.affiliation: Biomedical Research Group, Schools of Health Science and Science, Waterford Institute of Technology, Waterford, Ireland.
authors.forename: J P
authors.initials: JP
authors.lastname: Phelan
authors.affiliation: Biomedical Research Group, Schools of Health Science and Science, Waterford Institute of Technology, Waterford, Ireland.
authors.forename: M D
authors.initials: MD
authors.lastname: Ross
authors.affiliation: Departments of Vascular Surgery and Histopathology, Waterford Regional Hospital, Waterford, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Landers
authors.affiliation: Biomedical Research Group, Schools of Health Science and Science, Waterford Institute of Technology, Waterford, Ireland. Electronic address: mharrison@wit.ie.
authors.forename: M
authors.initials: M
authors.lastname: Harrison
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000601:surgery; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers
keywords: Biomarker; Carotid endarterectomy; Microparticles; Unstable plaque; Vascular