title: High levels of TSP1+/CD142+ platelet-derived microparticles characterise young patients with high cardiovascular risk and subclinical atherosclerosis.
abstract: 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.
authors.forename: Rosa
authors.initials: R
authors.lastname: Suades
authors.forename: Teresa
authors.initials: T
authors.lastname: Padró
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Alonso
authors.forename: Pedro
authors.initials: P
authors.lastname: Mata
authors.affiliation: Prof. Lina Badimon, Cardiovascular Research Center, C/ Sant Antoni Mª Claret 167, 08025 Barcelona, Spain, Tel.: +34 935565880, Fax: +34 935565559, E-mail: lbadimon@csic-iccc.org.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000367:Age Factors; D001013:Aorta, Thoracic; D001018:Aortic Diseases / Q000097:blood* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D058070:Asymptomatic Diseases; D015415:Biomarkers; D001792:Blood Platelets / Q000737:chemistry* / Q000648:ultrastructure; D002114:Calcinosis / Q000097:blood / Q000473:pathology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000737:chemistry*; D015331:Cohort Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000235:genetics; D008055:Lipids / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000737:chemistry / Q000209:etiology / Q000473:pathology; D015539:Platelet Activation; D012307:Risk Factors; D013925:Thromboplastin / Q000032:analysis*; D019700:Thrombospondin 1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D008055:Lipids; D019700:Thrombospondin 1; D013925:Thromboplastin
keywords: Atherothrombosis; circulating microparticles; platelets; risk factors; tissue factor