Abstract
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.
Highlights
Atherosclerosis can be defined as an inflammatory process: the exposure of extracellular matrix proteoglycans facilitates the subendothelial accumulation of low-density lipoprotein (LDL) which is exposed to oxidation
The aim of our study was to answer the following questions: (1) whether the presence of certain immune cells is associated with the presence of other pro- or antiinflammatory cells, for example, myeloid or plasmacytoid Dendritic cells extracellular matrix (ECM) (DC) with proinflammatory T cells or anti-inflammatory Regulatory T-cells (Tregs), and (2) whether the expression of functional molecules such as HLA-DR, CD25, and different chemokine receptors which might be involved in the attraction of circulating immune cells correlates with the plaque stability
The frequencies of different immune cells as well as functional markers were compared between unstable plaques (n = 15), stable plaques (n = 14), and vessels without any signs of atherosclerosis that served as control (n = 12)
Summary
Atherosclerosis can be defined as an inflammatory process: the exposure of extracellular matrix proteoglycans facilitates the subendothelial accumulation of low-density lipoprotein (LDL) which is exposed to oxidation. After migration into the intima, monocytes differentiate into macrophages which take up oxidized lipids and thereby transform into foam cells. The growing accumulation of cell debris and lipids leads to the formation of a necrotic plaque core. Smooth muscle cells migrate from the media into the intima where they produce extracellular matrix (ECM) proteins which compose a fibrous cap covering the plaque core, thereby stabilizing the atheroma (plaque stabilization). Macrophages lead to the thinning of this fibrous cap through the release of matrix metalloproteinases which is the prerequisite of plaque rupture (plaque destabilization). It has been unraveled that certain autoantigens like oxLDL might be the trigger for chronic inflammation in atherosclerosis. Autoantigens are presented in atherosclerotic lesions by antigen-presenting cells (APC) like macrophages
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