Coincidentally, one of the central contributors to our findings is the NLRP3 inflammasome, a known linchpin connecting metabolic stress to vascular inflammation.27,28 Using systemic NLRP3 knockout in ApoE-/-NLRP3-/- mice and endothelial-specific NLRP3 knockdown models, we confirmed the role of NLRP3 in driving endothelial pyroptosis and the progression of atherosclerosis. This evidence concerns the gene APOE and atherosclerosis.