793S troke is one of the major causes of death and disability worldwide. Approximately 85% of all strokes are ischemic, and 20% to 30% of these are caused by carotid atherosclerosis. Moderate-to high-grade carotid artery stenosis can be detected in 1% to 3% of adults, and the incidence increases with age. [1][2][3] Along with the degree of stenosis, inflammation and plaque composition are important in predicting the risk of clinical symptoms. 4 The atherosclerotic plaque is composed of infiltrating inflammatory cells (eg, monocytes/macrophages, T cells, and dendritic cells [DCs]), smooth muscle cells, and lipids. Plaques prone to rupture have thin fibrous caps and high-grade inflammation. The balance between pro-and anti-inflammatory mediators is therefore of major importance for the fate of the plaque and for the occurrence of adverse events.
5,6Background and Purpose-Interleukin (IL)-23 is a cytokine in the IL-12 family, mainly produced by antigen-presenting cells with a central role in inflammation. We hypothesize that IL-23 is also important in atherogenesis and investigate this in a population with carotid atherosclerosis. Methods-Plasma levels of IL-23 were measured in patients with carotid artery stenosis and in healthy controls. The mRNA levels of IL-23 and its receptor, IL-23R, were measured in atherosclerotic plaques, nonatherosclerotic vessels, peripheral blood mononuclear cells, and plasmacytoid dendritic cells. Results-Our findings were as follows: (1) patients with carotid atherosclerosis (n=177) had significantly raised plasma levels of IL-23 when compared with healthy controls (n=24) with particularly high levels in those with the most recent symptoms. (2) mRNA levels of IL-23 and IL-23R were markedly increased in carotid plaques (n=68) when compared with nonatherosclerotic vessels (n=8-10). Immunostaining showed colocalization to plaque macrophages. (3) Patients with carotid atherosclerosis had increased mRNA levels of both IL-23 and IL-23R in plasmacytoid dendritic cells, but not in peripheral blood mononuclear cells. (4) 14-16 Thus, patients with peripheral arterial disease have raised serum levels of IL-23, and increased IL-23 expression is seen in human carotid lesions.14,16 Zhang et al 17 showed that carriers of a polymorphism in the IL-23R gene, which also gave increased expression of IL-23R in peripheral blood mononuclear cells (PBMCs), had increased risk of coronary artery disease. However, decreased IL-23 in PBMCs from patients with coronary artery disease has also been reported. 18 In a mouse model of ischemic stroke, IL-23 levels were upregulated in both the circulation and in the brain. 15 However, the role for IL-23 in atherosclerosis is still unclear.In this study, we examined the expression of IL-23 in patients with carotid atherosclerosis both systemically and within the atherosclerotic plaque as well as its relation to adverse events during follow-up. We also examined the effect of IL-23 in PBMCs and monocytes from patients with carotid atherosclerosis and healthy controls.
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