Increased circulating monocyte activation in patients with unstable coronary syndromes

Objectives The primary objective of this research was to assess the activat ion level of circulating monocytes in patients with unstable angina. Background Markers of systemic inflammatory responses are increased in pati ents with unstable coronary syndromes, but the activation state and invasiv e 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 u sed to assess spontaneous cellular migration rates. In study 2, optical ana lysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a c ellular activation marker. Results Increased rates of spontaneous monocyte migration (p<0.01) were det ected in patients with unstable angina (UA) (Canadian Cardiovascular Societ y [CCS] angina class IV) on comparison to patients with acute myocardial in farction (MI), stable angina (CCS angina classes I to III) or normal donors . No significant increase in lymphocyte migration was detected in any patie nt category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparis on with MCs from normal volunteers (p<0.001). A concomitant reduction in th e NIC response to activation was detected (p<0.05). Conclusions Using two complementary assays, activated monocytes with increa sed invasive capacity were detected in the circulation of patients with uns table angina. This is the first demonstration of increased monocyte invasiv e potential in unstable patients, raising the issue that systemic inflammat ion may both reflect and potentially, drive plaque instability. (J Am Coll Cardiol 2001;38:1340-7) (C) 2001 by the American College of Cardiology.