Lipidomics reveals the dysregulated ceramide metabolism in oxidized low‐density lipoprotein‐induced macrophage‐derived foam cell

Abstract Atherosclerosis (AS) is associated with increasing lipid peroxidation. Oxidative modification of low‐density lipoproteins (ox‐LDL) is one most important factors contributing to the pathogenesis and clinical features of AS. The lipid composition influenced by ox‐LDL is not known clearly. In this work, a UHPLC/Orbitrap MS‐based lipidomics approach integrated pathway analysis was performed to advance understanding of the lipid composition and feature pathway in an ox‐LDL‐induced foamy macrophage cell. In the lipid metabolic profiling, 196 lipid species from 15 (sub)classes were identified. Lipid profiling indicated that increasing ox‐LDL caused lipid metabolic alternations, manifesting as phospholipids being down‐regulated and sphingolipids being up‐regulated. Pathway analysis explored glycerophospholipid and sphingolipid metabolism, which was involved in atherogenic changes. Notably, dysregulated ceramide metabolism was a typical feature of foamy cell formation. qRT‐PCR analysis was conducted to explore the differentially expressed genes. It indicated that ceramide metabolic balance might be disordered, performing higher synthesis and lower hydrolysis, with the ratio of SMPD1/SGMS2 being significantly up‐regulated ( p < 0.05) in the ox‐LDL induced group. Our work offers a comprehensive understanding of macrophage‐derived foam cells and screen feature pathways associated with foamy cell formation, which provides a reference for the clinic diagnosis of AS and drug interventions.