Circulating microparticles (cMPs) play important roles in cellular crosstalk and are messengers of cell activation. We have previously reported that platelet-released microparticles (pMPs) stimulate thrombosis and that lipid-lowering treatment as per guidelines in patients with familial hypercholesterolaemia (FH) is not sufficiently effective in reducing pro-inflammatory cell activation and, consequently, CD45+/CD3+-lymphocyte-derived cMP shedding. FH patients, due to life-long vascular exposure to high LDL-cholesterol levels, are at high cardiovascular risk (HCVR) and develop premature coronary artery disease. Our objectives were to investigate a) whether patients with HCVR have cMPs with a prothrombotic phenotype, and b) whether patients with magnetic resonance imaging (MRI) evidence of lipid-rich atherosclerotic lesions have a specific cMP profile regarding prothrombotic protein cargos. cMPs were isolated from HCVR-patients and from age/gender/treatment-matched control patients. cMP phenotype was characterised by triple-labelling flow cytometry. HCVR--patients have higher numbers of pMPs derived from activated platelets as well as of tissue factor-rich microparticles (TF+-cMPs) than controls (P< 0.0001). TF+-cMPs showed procoagulant activity, which associate with atherosclerotic plaque burden, indicating that TF in the cMPs is functional. In HCVR-patients, overall TF+-cMPs (monocyte-derived [CD142+/CD14+] and platelet-derived [CD142+/TSP1+]) and activated pMPs directly correlate with MRI-detected lipid-rich atherosclerotic plaques while inversely correlate with MRI-detected calcified plaques. C-statistics analysis showed that prothrombotic cMPs add significant prognostic value to a risk factor model for the prediction of lipid-rich plaques. In conclusion, the activation status of blood cells in HCVR-patients differed markedly from controls as shown by higher circulating levels of prothrombotic and TF+-cMPs. Prothrombotic cMP numbers identify subclinical atherosclerotic plaque burden.
Keywords: Atherothrombosis; circulating microparticles; platelets; risk factors; tissue factor.