Autophagy is associated with cell fate in the process of macrophage-derived foam cells formation and progress

Background: autophagy participates in plaque formation and progression; however,its association with foam cells' fate is unknown. to investigate autophagy features and its effect on the fate of different-stage macrophage foam cells (fcs). different-stage fcs were obtained through incubation of thp-1 macrophages (thp-m) with oxidized low-density lipoprotein ldl (oxldl,80 μg/ml) for various durations (0-72 h). autophagy in thp-1 macrophage fcs and in apoe-/- mice was regulated by rapamycin (80 ug/ml) or 3-ma (10 mm). lipid droplet accumulation,lc3 i/ii,p62 expression level,and autophagic flux were measured. vascular ultrasound,tunel,ihc,and dhe staining were used to detect the artery plaques in apoe-/- mice. results: in early-stage fcs,the amount of autophagosomes gradually increased,and autophagic flux intensity accelerated,but in mid-late stage fcs,autophagic flux was suppressed. for early stage fcs,treatment with autophagy activator rapamycin markedly decreased intracellular lipid content and prevented them from transforming into foam cells,while the autophagy inhibitor 3-ma considerably increased the intracellular lipid-droplet accumulation. during the process of foam cell development,upregulating autophagy not only reduced intracellular lipid-droplet accumulation,but also inhibited cell apoptosis through clearing dysfunctional mitochondria and lowering intracellular ros level. the in vivo experiments produced consistent results that rapamycin administration in apoe-/- mice reduced the death rate of macrophages and delayed plaque progression. conclusions: the fate of macrophage fcs was associated with autophagy. early autophagy enhancement inhibits the formation and progression of macrophage fcs and prevents atherosclerosis. © 2016 the author(s).