title: Monocyte subsets in coronary artery disease and their associations with markers of inflammation and fibrinolysis.
abstract: OBJECTIVE
  The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets.
  
  
  RESULTS
  Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKKβ) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2- (Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2 (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls.
  
  
  CONCLUSIONS
  There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis.
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, United Kingdom. Electronic address: e.shantsila@bham.ac.uk.
authors.forename: Eduard
authors.initials: E
authors.lastname: Shantsila
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, United Kingdom.
authors.forename: Luke D
authors.initials: LD
authors.lastname: Tapp
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, United Kingdom.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Wrigley
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, United Kingdom.
authors.forename: Burak
authors.initials: B
authors.lastname: Pamukcu
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, United Kingdom.
authors.forename: Stavros
authors.initials: S
authors.lastname: Apostolakis
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, United Kingdom.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoro-García
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, United Kingdom.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification* / Q000502:physiology*
chemical_list: D015415:Biomarkers
keywords: Coronary artery disease; Interleukin-6 receptor; Monocyte subsets; Monocytes