摘要
This study investigated the effects and mechanisms of 7-ketocholesterol in promoting macrophage foaming and inflammation.Single-cell RNA sequencing showed that dietary cholesterol oxidation products increased the inflammatory macrophage and Trem2high macrophage numbers in the atherosclerotic aorta of ApoE-/-mice.Enrichment analysis demonstrated activation of inflammation-related pathways(NF-κB pathway and NLRP3 inflammasome)in inflammatory macrophages and cholesterol metabolism-related pathways(LDLR and ABCG1)in Trem2high macrophages.An oxidized-LDL-treated macrophage model was employed to verify the effects and mechanisms of 7-KC on macrophage inflammation and foam cell formation.7-KC promoted the inflammation and M1 polarization of macrophage in association with the activations of the NF-κB pathway and NLRP3 inflammasome.Furthermore,7-KC-mediated excessive cholesterol accumulation was attributed to enhanced cholesterol uptake rather than inhibition of cholesterol efflux.Consequently,LDLR expression was up-regulated by 7-KC,while no significant effect on ABCG1 expression was observed.
基金
supported by the Zhejiang Provincial Natural Science Foundation of China[Grant No.LD21C200001 and LY24C200003]
the National Natural Science Foundation of China[Grant No.32072179].
