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Fig. 7
Working model of the proatherogenic properties of ChA. ChA is an end product of cholesteryl linoleate oxidation, generated in the arterial intima. Because of its amphiphilic properties, ChA can be detected in the plasma of CVD patients. The presence of ChA in circulation can imprint an inflammatory phenotype in the circulating monocytes and neutrophils (1), conditioning the immunological response in the arterial intima. ChA promotes the recruitment of innate immune cells, neutrophils, and monocytes into the vasculature (2). Here, neutrophils in the presence of ChA secret IL-1β, which can interfere with monocyte/macrophage priming. Monocytes differentiated in the presence of ChA are activated, increasing the secretion of inflammatory cytokines: IL-1β, IL-6, and IL-10 (3). In activated macrophages, ChA induces lipid accumulation (foam cells) and lysosomal dysfunction, conferring then the second signal necessary for IL-1β secretion mediated by inflammasome activation (4). IL-1β can initiate a propagation loop of the inflammation, increasing the macrophage secretion of IL-6 and TNF-α. On the other hand, dysfunctional lysosomes will decrease the clearance capacity of macrophages, leading to lipid accumulation in the arterial intima.