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.