title: Expression of stromal cell-derived factor-1 receptors CXCR4 and CXCR7 on circulating platelets of patients with acute coronary syndrome and association with left ventricular functional recovery.
abstract: BACKGROUND
  Surface expression of stromal cell-derived factor-1 (SDF-1) on platelets is enhanced during ischaemic events and might play an important role in peripheral homing and myocardial repair. As SDF-1 effects are mediated through CXCR4/CXCR7, we investigated platelet expression of SDF-1/CXCR4/CXCR7 in patients with coronary artery disease (CAD).
  
  
  RESULTS
  Expression of SDF-1, CXCR4, and CXCR7 in platelets was investigated by western blot analysis, immunofluorescence confocal microscopy, and flow cytometry among healthy subjects and patients with acute coronary syndrome (ACS) and stable CAD. In a cohort study, platelet surface expression of CXCR4, CXCR7, and SDF-1 was measured in 215 patients with symptomatic CAD (stable CAD = 112, ACS = 103) at the time of percutaneous coronary intervention. Course of left ventricular ejection fraction (LVEF) was followed up during intrahospital stay and at 3 months. Both CXCR4 and CXCR7 are surface expressed on human platelets and to a higher degree in CAD patients when compared with healthy controls. Platelet surface expression of CXCR7 but not CXCR4 was enhanced in patients with ACS when compared with patients with stable CAD (mean fluorescence intensity 17.8 vs. 15.3, P = 0.004 and 29.0 vs. 26.3, P = 0.122, respectively). CXCR4 and CXCR7 significantly correlated with their ligand SDF-1 on platelets (ρ = 0.273, P < 0.001 and ρ = 0.454, P < 0.001, respectively). Additionally, high CXCR7 expression above the median correlated with the absolute improvement of LVEF% after 5 days and 3 months (46.2, 49.8, 53.7; P = 0.003).
  
  
  CONCLUSIONS
  These findings indicate that platelet surface expression of CXCR4 and CXCR7 might differentially contribute to SDF-1-mediated effects on regenerative mechanisms following ACS. Studies are warranted to further evaluate the regulatory mechanisms of CXCR4/-7 expression and its prognostic impact on CAD.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Tübingen, Tübingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rath
authors.forename: Madhumita
authors.initials: M
authors.lastname: Chatterjee
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.forename: Karin
authors.initials: K
authors.lastname: Müller
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mack
authors.forename: Angela
authors.initials: A
authors.lastname: Bongartz
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
mesh_terms: D054058:Acute Coronary Syndrome / Q000378:metabolism*; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
chemical_list: C501896:ACKR3 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4
keywords: Acute coronary syndrome; CXCR4; CXCR7; SDF-1