[Trimetazidine reduces cholesterol content of foam cells by up-regulating autophagy and macrophage extracellular traps, and inhibiting inflammasome].

Objective To explore the effects of trimetazidine (TMZ) on the foam cell formation and its underlying mechanism in oxidized low-density lipoprotein (ox-LDL)-induced macrophages. Methods RAW264.7 cells were stimulated with ox-LDL to establish a foam cell model derived from macrophages. In the experiment, the foam cells were divided into control group (medium), model group (ox-LDL 60 μg/mL), chloroquine (CQ) group (ox-LDL 60 μg/mL combined with CQ 10 mmol/L) and TMZ group (ox-LDL 60 μg/mL combined with TMZ 80 μmol/L, CQ 10 mmol/L). The formation of foam cells was measured by oil red O staining. The levels of total cholesterol (TC) and free cholesterol (FC) in the foam cells were detected using ELISA. Autophagy was observed using MDC staining. Picogreen staining and quantitative fluorescence were performed to detect the formation of macrophage extracellular traps (MET). Then, the mRNA expression of LC3B, P62, inflammasome (NLRP3, ASC, caspase-1) and cholesterol efflux-related genes (ABCA1, ABCG1) were examined by real-time quantitative PCR. Results Compared with the model group, the expression of LC3B mRNA increased significantly, and P62 expression decreased in TMZ combined with CQ group. Meanwhile, the levels of TC, FC, CE/TC, and the expression of NLRP3, ASC, caspase-1 in TMZ combined with CQ group were reduced obviously. Furthermore, the formation of MET in TMZ combined with CQ group was promoted. However, the CQ group showed the opposite results. Conclusion Trimetazidine promotes cholesterol efflux in foam cells via activating autophagy and increasing the formation of MET, as well as inhibiting NLRP3 inflammasome.