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J Am Coll Cardiol, 2006; 48:70-80, doi:10.1016/j.jacc.2006.01.078 (Published online 9 June 2006).
© 2006 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Decrease in Circulating Myeloid Dendritic Cell Precursors in Coronary Artery Disease

Atilla Yilmaz, MD*,*, Jana Weber*, Iwona Cicha, PhD*, Christian Stumpf, MD*, Michael Klein, MD{dagger}, Dieter Raithel, MD{dagger}, Werner G. Daniel, MD* and Christoph D. Garlichs, MD*

* Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany
{dagger} Department of Vascular Surgery, Clinic Nuremberg, Nuremberg, Germany.

Manuscript received November 4, 2005; revised manuscript received January 3, 2006, accepted January 9, 2006.

* Reprint requests and correspondence: Dr. Atilla Yilmaz, Medical Clinic II, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. (Email: A.Yilmaz.med2.uni-erlangen{at}email.de).

OBJECTIVES: We analyzed the frequency of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) precursors in blood of patients with coronary artery disease (CAD) and in atherosclerotic carotid plaques of patients with cerebrovascular disease (CVD).

BACKGROUND: Circulating DC precursors are reduced in several autoimmune diseases. Atherosclerosis has features of an autoimmune disease, such as the presence of autoantibodies or autoreactive T cells. Tissue-resident DCs were previously described in atheromata, and it is assumed that they are important for the activation of T cells against autoantigens there.

METHODS: Circulating mDC and pDC precursors were flow cytometrically detected in healthy controls (n = 19), CAD patients with stable (n = 20) and unstable angina pectoris (n = 19), and acute myocardial infarction (n = 17). In human carotid plaques (n = 65), mDC and pDC precursors were identified immunohistochemically.

RESULTS: Circulating mDC precursors were significantly reduced in patients with stable angina pectoris (0.19%, p = 0.04), unstable angina pectoris (0.16%, p = 0.004), and acute myocardial infarction (0.08%, p < 0.001) compared with control patients (0.22% of peripheral blood mononuclear cells). In contrast, pDC numbers were not significantly altered. Circulating mDC precursors inversely correlated with high-sensitivity C-reactive protein (r = –0.38, p = 0.001) or interleukin-6 (r = –0.42, p < 0.001). In contrast to pDC, significantly more mDC precursors were observed in vulnerable carotid plaques (24, 0.25 mm2; n = 31; p = 0.003) than in stable ones (6.4, 0.25 mm2; n = 34).

CONCLUSIONS: Similar to autoimmune diseases, circulating mDC precursors were significantly reduced in patients with CAD. The emergence of mDC precursors in vulnerable plaques suggests their recruitment into atheromata as a possible reason for their decrease in blood. In contrast, no significant association of circulating pDC precursors with atherosclerosis was observed.

Abbreviations and Acronyms
  AMI = acute myocardial infarction
  BDCA = blood dendritic cell antigens
  CAD = coronary artery disease
  CRP = C-reactive protein
  DC = dendritic cell
  FITC = fluorescein isothiocyanate
  GP = glycoprotein
  HLA = human leukocyte antigen
  hsCRP = high-sensitivity C-reactive protein
  HSP = heat shock protein
  IL = interleukin
  mDC = myeloid dendritic cell
  MI = myocardial infarction
  MIP = macrophage inflammatory protein
  oxLDL = oxidized low-density lipoprotein
  PBMC = peripheral blood mononuclear cell
  PCI = percutaneous coronary intervention
  pDC = plasmacytoid dendritic cell
  PE = phycoerythrin
  SAP = stable angina pectoris
  UAP = unstable angina pectoris




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