Lipid raft redox signaling platforms in vascular dysfunction: Features and mechanisms

Lipid rafts (LRs) play essential roles in transmembrane signal transduction. Upon death factor stimulation, individual LRs cluster to recruit NADPH oxidase subunits and related proteins in vascular endothelial cells, forming LR redox signaling platforms, which ultimately results in increased production of reactive oxygen species in endothelial cells and impaired endothelial function. Mechanistically, ceramide generated from the hydrolysis of sphingomyelin by lysosomal acid sphingomyelinase spontaneously fuses to form ceramide-enriched macrodomains, which are critical contributors to the formation of LR redox signaling platforms. These LR signaling platforms play important roles in the development of endothelial dysfunction or injury upon pathologic insults.