title: Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina.
abstract: BACKGROUND
  Platelet activation plays a pivotal role in the pathogenesis of acute coronary disease. Monocytes are involved in the progression of atherosclerosis and are potent activators of blood coagulation through their ability to synthesize tissue factor (TF). The aim of this study was to compare markers of monocyte and coagulation activation in the systemic blood of patients with unstable angina, acute myocardial infarction, or stable angina.
  
  
  RESULTS
  We studied 26 patients with unstable angina (10 +/- 5 hours after the onset of the last episode of pain), 18 patients with acute myocardial infarction (5 +/- 4 hours after the onset of pain), and 34 patients with stable angina. We measured levels of TF expression in peripheral blood mononuclear cells (isolated by gradient centrifugation and incubated for 16 hours, with or without endotoxin stimulation), levels of plasma prothrombin fragment 1 + 2 (F1 + 2), and levels of fibrinogen in peripheral blood. In patients with unstable angina, both stimulated and unstimulated cells exhibited higher levels of TF expression than in patients with stable angina (P = .0001). In patients with acute myocardial infarction, monocyte TF activity did not differ from that in patients with stable angina. Mean levels of F1 + 2 and of fibrinogen did not differ significantly between groups. Only in the unstable angina group, a modest correlation was found between fibrinogen (r = .72, P = .005) and F1 + 2 levels (r = .54, P = .001) levels and the degree of monocyte TF expression. In patients with unstable angina, monocyte TF expression (both stimulated and unstimulated, assessed by biological activity and by antigen techniques) and fibrinogen levels were correlated with the time elapsed from the beginning of the most recent episode of pain (.61 < r < .72, .02 < P < .0001). By contrast, there was no correlation between these variables and the time from onset of pain in patients with acute myocardial infarction.
  
  
  CONCLUSIONS
  A time-dependent activation of systemic monocytes and a time-dependent increase in fibrinogen levels occurs in unstable angina but not in myocardial infarction. These findings provide further evidence that a specific inflammatory process occurs in unstable angina. Further studies are required to determine whether monocyte activation is a cause or a consequence of plaque instability in patients with unstable angina and to clarify the interrelations between platelet and monocyte activation in these circumstances.
authors.affiliation: Laboratoire d'Hématologie, Hôpital Cardiologique, Lille, France.
authors.forename: B
authors.initials: B
authors.lastname: Jude
authors.forename: B
authors.initials: B
authors.lastname: Agraou
authors.forename: E P
authors.initials: EP
authors.lastname: McFadden
authors.forename: S
authors.initials: S
authors.lastname: Susen
authors.forename: C
authors.initials: C
authors.lastname: Bauters
authors.forename: P
authors.initials: P
authors.lastname: Lepelley
authors.forename: C
authors.initials: C
authors.lastname: Vanhaesbroucke
authors.forename: P
authors.initials: P
authors.lastname: Devos
authors.forename: A
authors.initials: A
authors.lastname: Cosson
authors.forename: P
authors.initials: P
authors.lastname: Asseman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000097:blood*; D000789:Angina, Unstable / Q000097:blood*; D001777:Blood Coagulation; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009203:Myocardial Infarction / Q000097:blood*; D010446:Peptide Fragments / Q000378:metabolism; D011446:Prospective Studies; D011516:Prothrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D005340:Fibrinogen; D013925:Thromboplastin