Journal
THROMBOSIS AND HAEMOSTASIS
Volume 114, Issue 6, Pages 1310-1321Publisher
GEORG THIEME VERLAG KG
DOI: 10.1160/TH15-04-0325
Keywords
Atherothrombosis; circulating microparticles; platelets; risk factors; tissue factor
Categories
Funding
- Plan Estatal de I+D+I - Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa) [SAF2013-42962-R, AGAUR-2014SGR1303, Tercel-RD/12/0019/0026, RIC-RD12/0042/0027]
- Instituto Salud Carlos III (ISCIII) [FIS-PI13/02850]
- Associacio Esportiva Jordi Pitarque Cepria
- IC-Fundacion Jesus Serra to the Cardiovascular Research Chair-UAB
- [SAFE-T-No115003 IMI-JU]
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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.
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