SMPD1 and endothelial dysfunction: In this study, we generated EC-specific Smpd1 transgenic mice (Smpd1trg/ECcre) and examined whether the EC-specific overexpression of the Smpd1 gene could enhance the production of ceramide and the formation of MR redox signaling platforms, promote the activation of endothelial NLRP3 inflammasomes, and thereby result in endothelial dysfunction and atherogenesis.