title: Growing thrombi release increased levels of CD235a(+) microparticles and decreased levels of activated platelet-derived microparticles. Validation in ST-elevation myocardial infarction patients.
abstract: BACKGROUND
  Local 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.
  
  
  OBJECTIVE
  To investigate the specific phenotype of the cMPs released by growing thrombi.
  
  
  METHODS
  cMPs 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 ex vivo 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).
  
  
  RESULTS
  The levels of annexin V(+) 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 interval 0.889-1.000; P < 0.001).
  
  
  CONCLUSIONS
  Glycophorin-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.
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Suades
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Padró
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Vilahur
authors.affiliation: Department of Interventional Cardiology, Hospital Clinic, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Martin-Yuste
authors.affiliation: Department of Interventional Cardiology, Hospital Clinic, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sabaté
authors.affiliation: Acute and Intensive Cardiac Care Unit, Cardiology Department, Hospital Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sans-Roselló
authors.affiliation: Acute and Intensive Cardiac Care Unit, Cardiology Department, Hospital Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sionis
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.|Cardiovascular Research Chair, UAB, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003328:Coronary Thrombosis / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D005260:Female; D005434:Flow Cytometry; D006021:Glycophorins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D062645:Percutaneous Coronary Intervention; D010641:Phenotype; D015539:Platelet Activation; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D017131:Thrombectomy; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C409972:GYPA protein, human; D006021:Glycophorins; D013917:Thrombin
keywords: blood platelets; cell-derived microparticles; erythrocytes; hemodynamics; thrombosis