title: Impaired interaction of platelets with endothelial progenitor cells in patients with cardiovascular risk factors.
abstract: OBJECTIVE
  Recent studies indicate that platelets influence endothelial progenitor cell (EPC) recruitment to sites of vascular injury and promote their differentiation to an endothelial phenotype. Patients with cardiovascular risk factors (CVRF) demonstrate a reduced number and impaired function of EPC, as well as platelet hyper-reactivity. Therefore, we investigated the interaction of platelets and EPC from patients with CVRF.
  
  
  RESULTS
  Co-incubation of platelets and peripheral blood mononuclear cells, both from healthy volunteers, dose-dependently increased the number of adherent EPC. In contrast, patient-derived platelets failed to augment the number of adherent and migrating healthy and patient-derived EPC. However, co-incubation of platelets from healthy donors with mononuclear cells from patients with CVRF significantly enhanced the number of EPC, indicating that platelets from healthy volunteers are able to partially rescue the impairment of patient-derived EPC formation. Likewise, healthy donor-derived platelets augmented the impaired migration and clonal capacity of patient-derived EPC. Analysis of individual CVRF of platelet donors revealed that only diabetes mellitus inversely correlated with EPC number, colony formation and migration. The platelet supernatants from healthy volunteers that significantly increased EPC number contained IL-6, SDF-1, sCD40L and PDGF. While sCD40L and PDGF levels were comparable in platelet supernatants from healthy volunteers and patients with CVRF, the release of IL-6 and SDF-1 by patient-derived platelets was rather increased, thus, indicating that these soluble factors are not mediating the effect of platelet supernatants.
  
  
  CONCLUSIONS
  Healthy volunteer-derived platelets provide a source of soluble factors to improve the number and function of EPC from patients with cardiovascular risk factors, particularly diabetes mellitus.
authors.affiliation: Molecular Cardiology, Dept. of Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Dernbach
authors.forename: Voahanginirina
authors.initials: V
authors.lastname: Randriamboavonjy
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fleming
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Carmen
authors.initials: C
authors.lastname: Urbich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D016022:Case-Control Studies; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D054377:Chemokine CXCL12; D015850:Interleukin-6