TMAO has been shown to cause endothelial dysfunction by activating the NLRP3 inflammasome signaling pathway in both in vitro and in vivo studies.37,38 TMAO activates inflammatory cytokines and adhesion molecules, in part, through the mitogen-activated protein kinase and nuclear factor-κB signaling pathways.39 A study40 including healthy humans suggested that TMAO promotes age-related endothelial dysfunction via oxidative stress. This evidence concerns the gene NLRP3 and endothelial dysfunction.