Although other factors such as the accumulation of oxidized LDL in macrophages have been implicated in the initiation of atherosclerosis [1], [2], the data presented here may suggest an attractive alternative model, in which the dysregulation of SIRT1-AMPK-SREBP signaling and elevation of NLRP3 inflammasome components result in vascular lipid deposit and elicit inflammatory process in atherosclerosis related to diabetes (Fig. 9). The gene discussed is SIRT1; the disease is diabetes mellitus.