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Published on: January 28, 2020
Decrease in circulating myeloid dendritic cell precursors in coronary artery disease
Atilla Yilmaz1, Jana Weber, Iwona Cicha
1Medical Clinic II, University of Erlangen-Nuremberg, Erlangen, Germany. A.Yilmaz.med2.uni-erlangen@email.de
Insights
Circulating myeloid dendritic cell (mDC) precursors decrease in coronary artery disease (CAD) patients, correlating with inflammation. These mDC precursors are found in vulnerable atherosclerotic plaques, suggesting recruitment from the blood.
Area of Science:
- Immunology
- Cardiovascular Science
- Pathology
Background:
- Dendritic cells (DCs) are crucial immune cells.
- Reduced circulating DC precursors are noted in autoimmune diseases.
- Atherosclerosis shares autoimmune features, with DCs potentially activating T cells against autoantigens in plaques.
Purpose of the Study:
- To investigate the frequency of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) precursors in patients with coronary artery disease (CAD).
- To examine the presence of mDC and pDC precursors in atherosclerotic carotid plaques from patients with cerebrovascular disease (CVD).
Main Methods:
- Flow cytometry was used to quantify circulating mDC and pDC precursors in healthy controls and CAD patients (stable angina, unstable angina, acute myocardial infarction).
- Immunohistochemistry identified mDC and pDC precursors within human carotid plaques.
Main Results:
- Circulating mDC precursors were significantly reduced in CAD patients across all disease severities compared to controls.
- Reduced mDC precursor levels inversely correlated with inflammatory markers like high-sensitivity C-reactive protein and interleukin-6.
- mDC precursors were significantly more abundant in vulnerable carotid plaques than in stable ones, while pDC precursor numbers showed no significant alteration.
Conclusions:
- Circulating mDC precursor reduction in CAD patients mirrors findings in autoimmune diseases.
- The increased presence of mDC precursors in vulnerable plaques suggests their migration from blood to atheromata, explaining the peripheral decrease.
- Circulating pDC precursors did not show a significant association with atherosclerosis.
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.
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