title: Large platelets but not putative endothelial progenitor cells are associated with low strut coverage after drug-eluting stent implantation.
abstract: OBJECTIVE
  This study assessed whether different subsets of circulating endothelial and putative endothelial progenitor cells (CEC and EPC) correlate with stent strut coverage (SSC) using second generation optical coherence tomography (OCT).
  
  
  BACKGROUND
  Due to the lack of imaging modalities with a resolution down to the magnitude of a few cells, the influence of EPC on endothelialisation of drug-eluting stents has not been assessed in patients.
  
  
  METHODS
  In 37 patients, SSC of everolimus-eluting stents was assessed by OCT 5-7months after stent implantation. Different subsets of EPC (CD34(+)KDR(+), CD34(+)KDR(+)CD45(dim), CD133(+), CD3(+)CD31(+)), CEC (CD31(+)CD45(-)CD146(+)), and CD31(+)CD45(-)CD146(-) representing large platelets were analysed by flow cytometry, including viability analyses with 7-AAD. Statistical analysis comprised univariate regression analysis and multivariable models integrating OCT and flow cytometry data as well as clinical variables.
  
  
  RESULTS
  SSC and frequency of different cell types were highly comparable with previously published data. EPC defined in part by KDR expression were mostly non-viable. On univariate and in multivariable models, no association between EPC counts and strut coverage was detected. For CD31(+)CD45(-)CD146(-) counts, representing large platelets, an inverse relationship with strut coverage was identified by a multivariable regression model adjusting for age, sex, diabetes mellitus, NYHA and CCS class, CRP, serum triglycerides, glucose and creatinine (beta=-9.42, p=0.006).
  
  
  CONCLUSIONS
  There was no significant association between EPC or CEC and healing after drug-eluting stent implantation. Yet, CD31(+)CD45(-)CD146(-) cells were associated with low SSC. These data suggest that large platelets may represent a more important mediator of late stent endothelialisation than EPC.
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany. Electronic address: thomas.nuehrenberg@universitaets-herzzentrum.de.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Nührenberg
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stratz
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Amann
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Valina
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gick
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
authors.affiliation: Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre Johannes Gutenberg University Mainz, D-55101 Mainz, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Binder
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors.forename: Heinz Joachim
authors.initials: HJ
authors.lastname: Büttner
authors.affiliation: Universitäts-Herzzentrum Freiburg • Bad Krozingen, Klinik für Kardiologie und Angiologie II, Südring 15, D-79189 Bad Krozingen, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood; D001792:Blood Platelets / Q000166:cytology*; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation / Q000379:methods*; D054855:Drug-Eluting Stents; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D041623:Tomography, Optical Coherence / Q000379:methods; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D007166:Immunosuppressive Agents; D000068338:Everolimus; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: CEC; Drug-eluting stent; EPC; OCT; Strut coverage