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Introduction

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 which could be related to a specific cytokine profile.

Methods

Circulating EMPs and inflammatory cytokine levels were measured in seventy patients with significant carotid disease undergoing carotid endarterectomy and 20 healthy controls. Fifty one (73%) patients had symptomatic disease whilst 19 (27%) were asymptomatic. EMPs (CD31⁺/ Annexin V⁺ CD42b^-) were quantified using flow cytometry. Immunohistological analysis of carotid plaques for CD68⁺, CD206⁺ macrophages, TNF-α smooth muscle actin and osteopontin was performed, together with Alizarin red staining for detection of calcific deposits. Bioplex assays were used for cytokine analysis. Plaques were graded according to the American Heart Association plaque scoring system.

Results

Significantly higher EMP levels were observed in symptomatic patients compared to controls, p = 0.01, while no differences were noted in EMP levels in asymptomatic vs controls p = 0.11. The higher EMP levels appeared to associate with the unstable plaques which also had a significantly higher level of CD68⁺ macrophages compared to stable plaques (AHA I-IV) and higher circulating levels of Chemokine ligand-9 (CXCL-9) (p < 0.004). Of note, macrophage inhibitory factor (MIF) was among the chemokines that were elevated in the circulation of patients with stable plaques, whether a lack of this factor in unstable plaques has direct effects on phenotype remains to be elucidated. Other factors elevated in patients with stable plaques were IL-16, cutaneous T-cell attracting chemokine (CTACK), and stem-cell growth factor-b (SCGF-b) (p value of 0.05, 0.035 and 0.002 respectively).

Conclusion

Circulatory EMP and specific inflammatory cytokine levels are raised in patients with unstable plaques, while MIF, a potentially protective factor was elevated in serum of patients with stable plaques. These data could have major implications for the development of a diagnostic tool whereby EMPs together with markers of macrophage activity could act in a combined manner as biomarkers of plaque vulnerability and stroke susceptibility.