Cell-derived Microparticles as Part of Multimarker Strategies to Improve Vascular Risk Prediction

Antony Wekesa

    Research output: Types of ThesisDoctoral Thesis

    Abstract

    Candidate biomarkers should possess some of the following characteristics: identify individuals with disease, distinguish disease stage and monitor changes in health with treatment. There is increasing interest in the potential of cell-derived microparticles to act as sensitive biomarkers of vascular health status. Cell-derived microparticles (MP) are small (0.1-1.0 μm) plasma membrane derived vesicles shed into circulating blood by most cells, including platelets and endothelial cells. They may act not only as biomarkers but also mediators of vascular disease transferring biological agents that mediate inflammation, coagulation and vascular remodelling. In a series of studies, we have demonstrated that; 1. A number of small methodological studies undertaken suggest that flow cytometry can enumerate MP reproducibly but that variability can occur during sample processing through the double centrifugation protocol. Day to day biological variation also exists. 2. Annexin V+ MP (mainly of platelet origin) were higher in carotid artery disease cases compared to age-matched controls and added to predictive ability in a multivariable model. 3. CD31+CD41- endothelial MP (EMP) were higher in carotid artery patients with unstable plaques, classified post-surgery by immunohistochemistry. CD31+CD41- EMP, but not any subset of platelet MP, added to predictive ability in multivariable models to predict unstable plaques. 3. CD31+CD41- EMP in addition to other soluble markers were lower following a low carbohydrate diet that involved moderate reductions in body weight and waist circumference, with the effect size (Cohen’s d) greatest for CD31+CD41- EMP. 4. Other cellular vascular biomarkers were investigated, specifically endothelial progenitor cells and platelet monocyte aggregates but were not useful as biomarkers. A number of protein vascular biomarkers showed potential both in predicting disease and monitoring changes in health status, specifically the acute phase protein serum amyloid A. Despite the methodological difficulties that exist when enumerating MP, various subsets have shown potential as stand-alone biomarkers and in multivariable models. Future studies are justified including studies to examine the ability of MP to predict asymptomatic carotid artery disease and prospective studies to determine the prognostic ability.
    Original languageEnglish
    Awarding Institution
    Supervisors/Advisors
    • Harrison, Michael, Supervisor
    • O'Donovan, Orla, Supervisor
    • Cross, Keith S., Supervisor, External person
    Publication statusUnpublished - 2013

    Keywords

    • Multimarker strategies, Vascular risk prediction

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