title: Circulating platelet-progenitor cell coaggregate formation is increased in patients with acute coronary syndromes and augments recruitment of CD34+ cells in the ischaemic microcirculation.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the levels of platelet interaction with circulating CD34+ cells in patients with stable angina pectoris (SAP) and acute coronary syndromes (ACS) and to study the functional consequence of coaggregates formation in vitro and in vivo.
  
  
  RESULTS
  Platelet binding to circulating progenitor cells was defined by the presence of the platelet-specific marker glycoprotein Ib (CD42b) on the surface of CD34+ cells using flow cytometry. The percentage of CD34+/CD42b+ cell coaggregates was increased in patients with ACS (n = 162), and especially in patients with ST-elevation myocardial infarction (STEMI) (n = 44), compared with patients with SAP (n = 116; P < 0.001). In the ANCOVA analysis, platelet/CD34+ cell coaggregates were independently increased in ACS after adjustment for possible confounders. In a subgroup of our cohort, we also evaluated the levels of CD34+/CD133+/CD42b+ cell coaggregates, which were also significantly increased in ACS, and especially in STEMI (P < 0.05). Platelet/CD34+ cell coaggregates formation correlated with platelet activation (P = 0.001). In a prospective pilot study of patients with AMI (n = 40) using cardiac MRI, patients with increased baseline platelet/CD34+ cell coaggregates presented with a less myocardial infarct size and better left ventricular function at a 3-month follow-up compared with patients with lower coaggregates (P < 0.05 for all). The adhesion of platelet/CD34+ cell coaggregates onto the extracellular matrix and to endothelial monolayer was enhanced compared with CD34+ under high shear rates in vitro (P < 0.05) and within the microcirculation in mice after ischaemia/reperfusion injury as assessed by intravital microscopy (P < 0.05).
  
  
  CONCLUSIONS
  These findings imply that circulating platelet/CD34+ cell coaggregate levels are increased in ACS, especially in STEMI, which may be a novel mechanism of domiciliation of CD34+ progenitor cells to the injured microvasculature after acute myocardial infarction.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Otfried-Müller Str.10, 72076 Tübingen, Germany. konstantinos.stellos@kgu.de
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.forename: Florian
authors.initials: F
authors.lastname: Pfaff
authors.forename: Alexandra
authors.initials: A
authors.lastname: Elskamp
authors.forename: Saskia
authors.initials: S
authors.lastname: Sachsenmaier
authors.forename: Ruben
authors.initials: R
authors.lastname: Zachmann
authors.forename: Kimon
authors.initials: K
authors.lastname: Stamatelopoulos
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D000368:Aged; D060050:Angina, Stable / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001792:Blood Platelets / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D010865:Pilot Projects; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D013234:Stem Cells / Q000473:pathology*
chemical_list: D018952:Antigens, CD34; D016326:Extracellular Matrix Proteins; D010975:Platelet Aggregation Inhibitors
keywords: Acute coronary syndrome; Microcirculation; Platelets; Progenitor cells