title: Increased circulating monocyte activation in patients with unstable coronary syndromes.
abstract: OBJECTIVE
  The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina.
  
  
  BACKGROUND
  Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed.
  
  
  METHODS
  Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker.
  
  
  RESULTS
  Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05).
  
  
  CONCLUSIONS
  Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.
authors.affiliation: John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: C V
authors.initials: CV
authors.lastname: Zalai
authors.forename: M D
authors.initials: MD
authors.lastname: Kolodziejczyk
authors.forename: L
authors.initials: L
authors.lastname: Pilarski
authors.forename: A
authors.initials: A
authors.lastname: Christov
authors.forename: P N
authors.initials: PN
authors.lastname: Nation
authors.forename: M
authors.initials: M
authors.lastname: Lundstrom-Hobman
authors.forename: W
authors.initials: W
authors.lastname: Tymchak
authors.forename: V
authors.initials: V
authors.lastname: Dzavik
authors.forename: D P
authors.initials: DP
authors.lastname: Humen
authors.forename: W J
authors.initials: WJ
authors.lastname: Kostuk
authors.forename: G
authors.initials: G
authors.lastname: Jablonsky
authors.forename: P W
authors.initials: PW
authors.lastname: Pflugfelder
authors.forename: J E
authors.initials: JE
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Lucas
mesh_terms: D000704:Analysis of Variance; D000789:Angina, Unstable / Q000097:blood* / Q000145:classification / Q000188:drug therapy / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002462:Cell Membrane / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008560:Membrane Fluidity / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D009203:Myocardial Infarction / Q000097:blood / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors