Increased circulating monocyte activation in patients with unstable coronary syndromes

• Published in: Journal of the American College of Cardiology 2001-11, Vol.38 (5), p.1340-1347
• Main Authors: Zalai, Christian V, Kolodziejczyk, M.Dean, Pilarski, Linda, Christov, Alexander, Nation, Patric N, Lundstrom-Hobman, Marita, Tymchak, Wayne, Dzavik, Vladimir, Humen, Dennis P, Kostuk, William J, Jablonsky, George, Pflugfelder, Peter W, Brown, James E, Lucas, Alexandra
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Angina, Unstable - blood; Angina, Unstable - classification; Angina, Unstable - drug therapy; Angina, Unstable - immunology; Biological and medical sciences; Biomarkers - blood; Cardiology. Vascular system; Case-Control Studies; Cell Membrane - immunology; Cell Movement - immunology; Chemotaxis, Leukocyte - immunology; Coronary heart disease; Heart; Humans; Immunohistochemistry; Inflammation; Lipopolysaccharide Receptors - blood; Lipopolysaccharide Receptors - immunology; Lymphocyte Activation - immunology; Medical sciences; Membrane Fluidity - immunology; Monocytes - immunology; Myocardial Infarction - blood; Myocardial Infarction - immunology; Severity of Illness Index
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(01)01570-4

OBJECTIVES 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.