title: Monocyte-derived and CD34+/KDR+ endothelial progenitor cells in heart failure.
abstract: BACKGROUND
  Endothelial progenitor cells (EPCs) are known to be altered in heart failure (HF), but monocyte-derived EPCs in HF have not been assessed. We aimed to characterize monocyte-derived EPCs in systolic HF.
  
  
  RESULTS
  We recruited 128 subjects with systolic HF: 50 South Asian (SA), 50 white, and 28 African-Caribbean (AC), for interethnic comparisons. Additionally, SAs with HF were compared with 40 SAs with coronary artery disease (CAD) without HF (disease controls [DCs]) and 40 SA healthy controls (HCs). Counts of CD34(+) and kinase domain receptor (KDR)(+) monocytes attributed to specific monocyte subsets (CD14(++) /CD16(-) [Mon1], CD14(++)/CD16(+) [Mon2], and CD14(+)/CD16(++) [Mon3]) and monocyte expression of vascular endothelial growth factor (VEGF) receptor 1 were analyzed by flow cytometry. We also enumerated CD34(+)/KDR(+) EPCs derived from mononuclear cells ('classic' EPC definition).
  
  
  RESULTS
  SAs with HF had significantly reduced counts of CD34(+) monocytes, attributed to the Mon1 and Mon2 subsets. KDR(+) Mon1 counts were 4.5-fold increased in DCs as compared with HCs, but significantly reduced in HF subjects vs. DCs. VEGF receptor type 1 expression on Mon1 and Mon2 cells was significantly reduced in HF patients as compared with DCs. Also, CD34(+)/KDR(+) EPC numbers were reduced in HF subjects. Whites had significantly fewer KDR(+) Mon3 cells than ACs, but significantly more CD34(+) Mon2 cells than SAs and ACs. VEGF receptor type 1 expression by Mon1 cells was predictive for left ventricular ejection fraction after adjustment for ethnicity (β = - 0.25. P = 0.039). CD34(+) Mon2 counts correlated with measures of microvascular endothelial function, and were predictive of the future risk of hospital admission.
  
  
  CONCLUSIONS
  Circulating counts of monocyte-derived EPCs are significantly altered in HF, with significant ethnic differences in the levels of monocyte-derived EPCs.
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham             Primary Care Clinical Sciences, University of Birmingham, Birmingham, UK.
authors.forename: E
authors.initials: E
authors.lastname: Shantsila
authors.forename: B J
authors.initials: BJ
authors.lastname: Wrigley
authors.forename: A
authors.initials: A
authors.lastname: Shantsila
authors.forename: L D
authors.initials: LD
authors.lastname: Tapp
authors.forename: P S
authors.initials: PS
authors.lastname: Gill
authors.forename: G Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology*; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology*; D013234:Stem Cells / Q000276:immunology / Q000473:pathology*; D014463:Ultrasonography; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*
chemical_list: D018952:Antigens, CD34; D040301:Vascular Endothelial Growth Factor Receptor-2