RNA-seq of macrophages treated with or without MLN4924
MLN4924, a neddylation inhibitor with potential in cancer treatment, has anti - inflammatory effects. As atherosclerosis is an inflammatory disease related to autophagy and cell senescence, this study explored MLN4924's role in it. Focusing on foam cell formation, a key step in atherosclerosis, results showed MLN4924 downregulated scavenger receptors like CD36, and upregulated cholesterol efflux gene ABCA1. It also inhibited macrophage senescence and SASP - related factors, possibly via enhanced autophagy. Analyses revealed its impact on macrophage transcriptome and metabolism, with genes enriched in the PI3K - AKT pathway. MLN4924 inhibited AKT phosphorylation, regulated gene expression such as ABCA1, and modulated metabolite production. These suggest its potential as an anti - atherosclerotic agent for further research. Overall design: RNA sequencing analysis of macrophages treated with ox-LDL alone and macrophages treated with ox-LDL+MLN4924 at the 48th hour of transformation into foam cells