Decrease in Circulating Myeloid Dendritic Cell Precursors in Coronary Artery Disease
Received 4 November 2005; received in revised form 3 January 2006; accepted 9 January 2006. published online 12 June 2006.
Decrease in Circulating Myeloid Dendritic Cell Precursors in Coronary Artery Disease
Atilla Yilmaz, Jana Weber, Iwona Cicha, Christian Stumpf, Michael Klein, Dieter Raithel, Werner G. Daniel, Christoph D. Garlichs
Immunological mechanisms play a crucial role in atherosclerosis. We describe a significant reduction in circulating myeloid dendritic cell precursors in patients with coronary artery disease. In carotid plaques, a significant increase in myeloid dendritic cell precursors was associated with plaque vulnerability, suggesting their recruitment from blood into unstable atheromata. In contrast, the frequency of plasmacytoid dendritic cell precursors was not significantly altered in the circulation of patients with coronary artery disease or carotid plaques.
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.
ABSTRACT