Inflammasome Activation and Neutrophil Extracellular Traps in Atherosclerosis

The deposition of cholesterol containing cholesterol crystals and the infiltration of immune cells are features of atherosclerosis. Although the role of cholesterol crystals in the progression of atherosclerosis have long remained unclear, recent studies have clarified the involvement of cholesterol crystals in inflammatory responses. Cholesterol crystals activate the NLRP3 inflammasome, a molecular complex involved in the innate immune system. Activation of NLRP3 inflammasomes in macrophages cause pyroptosis, which is accompanied by the release of inflammatory cytokines such as IL-1 beta and IL-1 alpha . Furthermore, NLRP3 inflammasome activation drives neutrophil infiltration into atherosclerotic plaques. Cholesterol crystals trigger NETosis against infiltrated neutrophils, a form of cell death characterized by the formation of neutrophil extracellular traps (NETs), which, in turn, prime macrophages to enhance inflammasome-mediated inflammatory responses. Colchicine, an antiinflammatory drug effective in cardiovascular disease, is expected to inhibit cholesterol crystal-induced NLRP3 inflammasome activation and neutrophil infiltration. In this review, we illustrate the reinforcing cycle of inflammation that is amplified by inflammasome activation and NETosis.