Glutamine influx licenses macrophage glutaminolysis for restorative functions in atherosclerosis

Atherosclerotic plaque macrophages are key players at the site of disease, where metabolic reprogramming dictates whether they ameliorate or exacerbate pathogenesis. Here, we found that glutamine synthetase served as a metabolic rheostat controlling nutrient flux into cells in vitro, macrophage restorative functions in the context of atherosclerosis relied more heavily on glutamine influx and glutaminase activity. Cell-intrinsic regulation of glutaminolysis drives macrophage metabolic and transcriptional rewiring in atherosclerosis by diverting exogenous Gln flux to balance remodeling and restorative functions. Thus, we uncover a role of glutamine uptake upstream of glutaminolysis in atherosclerotic plaque development and stability.