title: Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis.
abstract: OBJECTIVE
  For the characterization of endothelial progenitor cells (EPCs), commonly the markers CD34 and KDR have been used. CD133+/CD34-/KDR+ cells may represent more immature 'early' progenitors. In patients with coronary artery disease (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN), which may mediate vascular calcification and abnormal repair. The aim of this study was to evaluate the expression of OCN+ 'early' EPCs in patients with risk factors (RFs) and a history of stable (history of stenting/coronary artery bypass grafting) or unstable CAD (myocardial infarction).
  
  
  RESULTS
  Medical history and blood samples from 282 patients (age 58 ± 16 years) with CAD or at least one RF (mean 2.5 ± 1.5) were analysed. For the analysis of EPC markers (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear cells was performed. Circulating OCN+/CD133+/CD34-/KDR+ cells (median counts [interquartile range] per 100 000 events) were 15 [4-41] in patients with RF (n = 199), 26 [1-136] in those with a history of stable (n = 57), and 246 [105-308] in those with a history of unstable CAD (n = 26; P < 0.001). The association with unstable CAD remained highly significant even after multivariate adjusting for RFs and the different characteristics of the groups. Osteocalcin positive 'early' EPCs trend to predict further events [HR for each doubling of the cell number: 1.20 (95% CI: 1.00-1.46), P = 0.06].
  
  
  CONCLUSIONS
  Circulating OCN+ 'early' EPCs are strongly associated with unstable CAD. Therefore, this particular subset of EPCs could mediate abnormal vascular repair and may help identifying patients with a more unstable phenotype of atherosclerosis.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic and College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Flammer
authors.forename: Mario
authors.initials: M
authors.lastname: Gössl
authors.forename: Robert Jay
authors.initials: RJ
authors.lastname: Widmer
authors.forename: Martin
authors.initials: M
authors.lastname: Reriani
authors.forename: Ryan
authors.initials: R
authors.lastname: Lennon
authors.forename: Darrell
authors.initials: D
authors.lastname: Loeffler
authors.forename: Sarah
authors.initials: S
authors.lastname: Shonyo
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000401:mortality / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011379:Prognosis; D013234:Stem Cells / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D015675:Osteocalcin; D040301:Vascular Endothelial Growth Factor Receptor-2