Mechanism study of ankyrin repeat and suppressor of cytokine signaling box containing 13 promoting atherosclerosis through snail family transcriptional repressor 2/solute carrier family 7 member 11 mediated ferroptosis
Objective Investigate the role of Ankyrin repeat and suppressor of cytokine signaling(SOCS)box containing 13(ASB13)in atherosclerosis(AS)and the underlying molecular mechanisms.Methods Apolipoprotein E gene knockout(ApoE-/-)mice were randomly divided into control group,AS group,sh-NC group,sh-ASB13 group and sh-ASB13+sh-snail family transcriptional repressor 2(SNAI2)group.Mice in control group were fed with standard diet,and the other4 groups were fed with high-fat diet for 8 weeks.In cell experiment 1,HUVECs were divided into cell control group,ox-LDL group,ox-LDL+si-NC group,ox-LDL+si-ASB13 group and ox-LDL+si ASB13+Erastin group.In cell experiment 2,HUVECs were divided into ox-LDL+si-NC group,ox-LDL+si-SNAI2 group and ox-LDL+si-ASB13+si-SNAI2 group.HE staining was used to evaluate the histopathological changes.CCK-8 was used to analyze cell viability.Western blotting was used to detect the protein expression levels of ASB13,SNAI2,solute carrier family 7 member 11(SLC7A11)and GPX4.Biochemical detection kit was used to detect the serum of lipid metabolites and Fe2+level.Results Results of animal experiments showed that compared with control group,serum level of HDL-C and expression levels of SLC7A11 and GPX4 protein in aortic tissues of AS group mice were significantly decreased,serum levels of LDL-C,TC,TG,Glu and Fe2+and expression levels of ASB13 protein in aortic tissues were increased(P＜0.05).Compared with sh-NC group,ASB13 knockdown inhibited atherosclerotic plaque formation in AS mice,and SNAI2 knockdown promoted atherosclerotic plaque formation.Results of cell experiments showed that compared with cell control group,ox-LDL treatment reduced the viability of HUVECs cells,increased expression levels of ASB13 protein and promoted lipid accumulation and ferroptosis;Silencing ASB13 elevated cell viability and reduced lipid accumulation and ferroptosis(P＜0.05).ASB13 ubiquitin lower expression levels of SNAI2 protein,while SNAI2 combined with SLC7A11 promoter to promote its transcription activation,raised expression levels of SLC7A11 protein.Compared with ox-LDL+si-NC group,SNAI2 silencing or iron death revulsant Erastin processing reversed ASB13 silence of HUVECs protection(P＜0.05).Conclusion Knockdown of ASB13 may promote atherosclerosis through SNAI2/SLC7A11-mediated ferroptosis.
AtherosclerosisAnkyrin repeat and suppressor of cytokine signaling box containing 13Snail family transcriptional repressor 2UbiquitinationFerroptosis
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