title: Inter-relationships of indices of endothelial damage/dysfunction [circulating endothelial cells, von Willebrand factor and flow-mediated dilatation] to tissue factor and interleukin-6 in acute coronary syndromes.
abstract: BACKGROUND
  Increased circulating endothelial cells (CECs, reflecting endothelial damage) in acute coronary syndromes (ACS) has been reported. However, the inter-relationships of indices of endothelial damage/injury with development of vascular (dys)function, plasma levels of tissue factor (TF, an index of coagulation) and interleukin-6 (IL-6, a pro-inflammatory cytokine) have not been investigated in ACS. We hypothesized that increased CECs can be related to impaired flow-mediated vasodilatation (FMD, an index of endothelial dysfunction) and elevated plasma von Willebrand factor (vWf, also marking endothelial damage/dysfunction), TF and IL-6 in patients with ACS.
  
  
  METHODS
  We studied 120 patients with ACS (80 acute myocardial infarction and 40 unstable angina; 86 male, age 65+/-12 years) and 40 matched patients with stable CAD and 40 healthy controls (HC) in a cross-sectional analysis. Plasma vWf, TF and IL-6 levels were measured by ELISA. CECs were quantified using epifluorescence microscope after immunomagnetic separation with CD146. Brachial artery FMD was assessed in a subset of 39 ACS patients.
  
  
  RESULTS
  ACS patients had significantly higher CECs, vWf, TF and IL-6 levels, but lower FMD, when compared to stable CAD and HC (all p<0.001) and all were inter-correlated significantly. In ACS, CECs was strongly correlated with FMD (r=-0.64, p<0.001) and TF (r=0.7, p<0.001). In stable CAD, significant correlations were again found between many indices, but on multivariate analysis, IL-6 and vWf were both independently related to FMD.
  
  
  CONCLUSIONS
  Increased CECs in ACS patients are closely associated with endothelial damage/dysfunction (vWf and FMD), coagulation (TF) and inflammation (IL-6). These inter-relationships support the concept of a central role of endothelial damage/injury in the activation of vascular and coagulation abnormalities in ACS.
authors.affiliation: Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK.
authors.forename: Kaeng W
authors.initials: KW
authors.lastname: Lee
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Blann
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D002637:Chest Pain / Q000097:blood; D003327:Coronary Disease / Q000097:blood*; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D013925:Thromboplastin / Q000032:analysis*; D014664:Vasodilation; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D014841:von Willebrand Factor; D013925:Thromboplastin