Expression of the NLRP3 Inflammasome in Carotid Atherosclerosis.

ABSTRACT

BACKGROUND: The aim of the present study was to investigate NLRP3 inflammasome expression in human carotid atherosclerotic plaques and its relationship to plaque vulnerability. METHODS: Carotid atherosclerotic plaques collected from 30 patients scheduled for carotid endarterectomy (CEA) were subjected to immunohistochemical, mRNA, and protein expression studies. Ten mesenteric arteries from intestinal cancer patients served as controls for the immunohistochemical studies. Twenty individuals who had no carotid stenosis or coronary artery stenosis served as controls for analyzing atherosclerotic risk factors and for enzyme-linked immunosorbent assay (ELISA) studies. Serum samples were collected from all patients to determine interleukin-1ß (IL-1ß) and IL-18 levels. RESULTS: The NLRP3 inflammasome signaling pathway components NLRP3, ASC, caspase-1, IL-1ß, and IL-18 were strongly expressed in carotid atherosclerotic plaques, but not in healthy mesenteric arteries. Immunohistochemical, mRNA, and protein expression studies revealed higher expression levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18 in unstable compared to stable plaques. The NLRP3 inflammasome was localized in the cytoplasm of macrophages and foam cells and was associated with cholesterol crystal clefts inside and outside of cells. ELISA showed that the serum levels of the cytokines IL-1ß and IL-18 were higher in the CEA group compared to controls. CONCLUSIONS: These results demonstrated for the first time the close relationship between the expression of NLRP3 signaling pathway and human carotid atherosclerotic plaques. NLRP3, ASC, caspase-1, IL-1ß, and IL-18 were associated with plaque vulnerability and atherogenesis. The serum levels of IL-1ß and IL-18 may be useful predictors of atherosclerosis.