Abstract-The

DC (dendritic cells) play an important role in the immune system. They invade peripheral tissues to detect harmful antigens, inducing a local immune response. Studies suggest that DCPs (dendritic cell precursors) might be reduced in AMI (acute myocardial infarction); however, the reason for their reduction is unknown yet. In the present study, circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs), tDCPs (total DCPs) and serum levels of TNFα (tumour necrosis factor α), IL (interleukin)-2, -4, -5, -6, -10 and -12 were analysed by flow cytometry in blood of patients with NSTEMI [non-STEMI (ST-segment elevation myocardial infarction)] (n=44) and STEMI (n=34) compared with controls with excluded CAD (coronary artery disease) (n=45). Post-mortem myocardial specimens of patients with AMI (n=12) and healthy myocardium of accident victims (n=10) were immunostained for mDCs (myeloid dendritic cells) T-cells and macrophages. Compared with controls, in patients with AMI a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.0001). The extent of the decrease was higher in STEMI than NSTEMI patients. Serum levels were significantly higher in patients with AMI compared with controls for IL-6, -10, -12 and TNFα (each P<0.03). Immunostaining revealed significantly higher number of DCs, T-cells and macrophages (each P<0.002) in infarcted than control myocardium. We show that circulating DCPs are significantly reduced in AMI, with a pronounced reduction in STEMI patients. This was accompanied by a significant increase of inflammatory serum cytokines in patients with AMI. Immunohistochemical analysis unravelled that the reduction of circulating DCPs might be due to recruitment into the infarcted myocardium.

Atherosclerosis is a chronic inflammatory disease of the arterial wall in which presentation of autoantigens by dendritic cells (DCs) leads to the activation of T cells. Anti-inflammatory cells like Tregs counterbalance inflammation in atherogenesis. In our study, human carotid plaque specimens were classified as stable (14) and unstable (15) according to established morphological criteria. Vessel specimens (n = 12) without any signs of atherosclerosis were used as controls. Immunohistochemical staining was performed to detect different types of DCs (S100, fascin, CD83, CD209, CD304, and CD123), proinflammatory T cells (CD3, CD4, CD8, and CD161), and anti-inflammatory Tregs (FoxP3). The following results were observed: in unstable lesions, significantly higher numbers of proinflammatory cells like DCs, T helper cells, cytotoxic T cells, and natural killer cells were detected compared to stable plaques. Additionally, there was a significantly higher expression of HLA-DR and more T cell activation (CD25, CD69) in unstable lesions. On the contrary, unstable lesions contained significantly lower numbers of Tregs. Furthermore, a significant inverse correlation between myeloid DCs and Tregs was shown. These data suggest an increased inflammatory state in vulnerable plaques resulting from an imbalance of the frequency of local pro- and anti-inflammatory immune cells.

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Plasma levels of novel biomarkers were significantly elevated (sST2, GDF-15, H-FABP, suPAR) or inversely downregulated (fetuin A) in patients with AMI compared to a control group with excluded coronary artery disease. Significant correlations with various clinical parameters and standard biochemical markers were found.