Predicting Carotid Artery Disease and Plaque Instability from Cell-derived Microparticles

Wekesa, A.L.; O'Donovan, O.; O'Brien, O.; Phelan, J.P.; Ross, M.D.; Harrison, M.; Wekesa, Anthony L; Cross, K.S.; O'Donovan, Orla; Dowdall, J.F.; O'Brien, O; Doyle, M.; Byrne, L.; Phelan, John P; Ross, Mark D; Landers, R.; Harrison, Michael

Abstract

Objectives
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.

Citation

Harrison, M., Wekesa, A., O'Donovan, O., O'Brien, O., Phelan, J., Ross, M., Wekesa, A. L., Cross, K., O'Donovan, O., Dowdall, J., O'Brien, O., Doyle, M., Byrne, L., Phelan, J. P., Ross, M. D., Landers, R., & Harrison, M. (2014). Predicting Carotid Artery Disease and Plaque Instability from Cell-derived Microparticles. European Journal of Vascular and Endovascular Surgery, 48(5), 489-495. https://doi.org/10.1016/j.ejvs.2014.08.007

• Journal Article Type: Article
• Acceptance Date: Aug 1, 2014
• Online Publication Date: Sep 10, 2014
• Publication Date: 2014-11
• Deposit Date: May 6, 2016
• Publicly Available Date: Apr 18, 2018
• Print ISSN: 1078-5884
• Electronic ISSN: 1532-2165
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 48
• Issue: 5
• Pages: 489-495
• DOI: https://doi.org/10.1016/j.ejvs.2014.08.007
• Keywords: Microparticles; unstable plaque; biomarker; vascular; carotid endarterectomy
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/10027
• Publisher URL: http://dx.doi.org/10.1016/j.ejvs.2014.08.007
• Contract Date: Apr 18, 2018