High levels of TSP1⁺/CD142⁺ platelet-derived microparticles characterise young patients with high cardiovascular risk and subclinical atherosclerosis^[*]

Summary

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

^* Presented in abstract form at the XXIV Congress of the International Society of Thrombosis and Haemostasis, Amsterdam, July 2^nd, 2013. Received a Young Investigator Award.

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