Growing thrombi release increased levels of CD235a(+) microparticles and decreased levels of activated platelet-derived microparticles. Validation in ST-elevation myocardial infarction patients
Por:
Suades, R, Padro, T, Vilahur, G, Martin-Yuste, V, Sabate, M, Sans-Rosello, J, Sionis, A, Badimon, L
Publicada:
1 oct 2015
Resumen:
BackgroundLocal fluid dynamics and exposed atherosclerotic lesions regulate thrombus formation. Activated cells in the attached thrombi release microparticles to the circulation (circulating microparticles [cMPs]); however, their phenotype is unknown.
ObjectivesTo investigate the specific phenotype of the cMPs released by growing thrombi.
Methods/patientscMPs released by thrombi growing in different well-characterized thrombogenic conditions were investigated. cMP contents just before and immediately after perfusion of the thrombogenic surfaces were analyzed by triple-labeling flow cytometry. cMPs were tested for their thrombin-generating capacity. The cMPs identified in the exvivo perfusion experiments were validated in blood of ST-elevation myocardial infarction (STEMI) patients undergoing thrombectomy and percutaneous coronary intervention. Culprit coronary blood (STEMI-CCB) and peripheral artery blood (STEMI-PAB) were simultaneously analyzed and compared with peripheral artery blood from age-matched controls (C-PAB) and peripheral artery blood from patients who had recovered from acute coronary syndrome (ACS) (pSTEMI-PAB).
ResultsThe levels of annexinV(+) cMPs significantly increased in blood collected after perfusion of the exposed thrombogenic surfaces. cMP release was directly related to the formed thrombus mass and the plasma procoagulant activity. Post-thrombus blood showed higher thrombin generation potential and contained higher levels of cMPs carrying glycophorin-A (CD235a(+); erythrocyte-derived microparticles [ErMPs]) than preperfusion blood (P<0.05), whereas the levels of cMPs carrying activated and adhesion platelet markers were decreased. STEMI-CCB and STEMI-PAB had significantly higher ErMP levels than control blood (P<0.005). ErMP levels were also significantly higher in STEMI-PAB than in pSTEMI-PAB, validating the experimental mechanistic studies and suggesting that ErMPs are markers of ongoing coronary thrombosis (C-statistics: 0.950; 95% confidence interval0.889-1.000; P<0.001).
ConclusionGlycophorin-A-rich microparticles are released from evolving growing thrombi into the distal perfusing blood, and can be measured in peripheral blood. CD235a(+) cMPs may constitute a novel systemic biomarker of ongoing thrombosis.
Filiaciones:
Suades, R:
CSIC ICCC, Cardiovasc Res Ctr, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Padro, T:
CSIC ICCC, Cardiovasc Res Ctr, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Vilahur, G:
CSIC ICCC, Cardiovasc Res Ctr, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Martin-Yuste, V:
Hosp Clin Barcelona, Dept Intervent Cardiol, Barcelona, Spain
Sabate, M:
Hosp Clin Barcelona, Dept Intervent Cardiol, Barcelona, Spain
Sans-Rosello, J:
Hosp Santa Creu & Sant Pau, Dept Cardiol, Acute & Intens Cardiac Care Unit, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Sionis, A:
Hosp Santa Creu & Sant Pau, Dept Cardiol, Acute & Intens Cardiac Care Unit, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Badimon, L:
CSIC ICCC, Cardiovasc Res Ctr, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
UAB, Cardiovasc Res Chair, Barcelona, Spain
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