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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, Dieter Raithel, MD, Werner G. Daniel, MD^_* and Christoph D. Garlichs, MD^_*

^_* Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany
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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