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ACUTE CORONARY SYNDROMES

Increased circulating monocyte activation in patients with unstable coronary syndromes

Christian V. Zalai, MSc^* , M. Dean Kolodziejczyk, MSc^* , Linda Pilarski, PhD^||, Alexander Christov, PhD^*, Patric N. Nation, DVM^¶, Marita Lundstrom-Hobman, PhD, Wayne Tymchak, MD, FRCP(C), FACC^#, Vladimir Dzavik, MD, FRCP(C), FACC^{# **}, Dennis P. Humen, MD, FRCP(C), FACC^{# ||}, William J. Kostuk, MD, FRCP(C), FACC, George Jablonsky, MD, FRCP(C), FACC, Peter W. Pflugfelder, MD, FRCP(C), FACC, James E. Brown, MD, FRCP(C), FACC and Alexandra Lucas, MD, FRCP(C), FACC^{*,* #}

^* John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada
Department of Medicine, University of Western Ontario, London, Ontario, Canada
Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada
^|| Department of Oncology, University of Alberta, Edmonton, Alberta, Canada
^¶ Department of Lab Animal Sciences, University of Alberta, Edmonton, Alberta, Canada
^# Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
^** Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Manuscript received January 25, 2001; revised manuscript received June 18, 2001, accepted July 12, 2001.

^* Reprint requests and correspondence: Dr. Alexandra Lucas, The John P. Robarts Research Institute, 100 Perth Drive, PO Box 5015, London, Ontario, Canada N6A 5K8
arl{at}rri.on.ca

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.

Abbreviations and Acronyms   ANOVA = analysis of variance   BSA = bovine serum albumin   CAD = coronary artery disease   CCS = Canadian Cardiovascular Society   CRP = C-reactive protein   DMEM = Dulbecco’s minimal essential medium   fMLP = formyl-methionyl-leucyl-phenylalanine   IHD = ischemic heart disease   IL = interleukin   LPS = lipopolysaccharides   MC = mononuclear cell   MCP-1 = macrophage chemoattractant protein-1   MI = myocardial infarction   OA = optical analysis   PBS = phosphate-buffered saline   PMA = phorbol-12-myristate-13-acetate   SAA = serum amyloid A protein   sCD14 = soluble CD14   UA = unstable angina

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