LncRNA MALAT1 mediates miR-17-5p/ABCA1 axis to inhibit the development of atherosclerosis
Objective To explore the effects of overexpression of IncRNA MALAT1 on the formation of atherosclerotic plaque,lipid accumulation and blood lipid levels in mice,and further explore the role of miR-17-5p/ABCA1 axis mediated by it.Methods MALAT1 overexpression lentivirus was injected into the tail vein of AS mice,and the expressions of MALAT1,miR-17-5p,and ABCA1 in mouse aorta and peritoneal macrophages were detected by using RT-qPCR and Western blot.HE staining was used to observe the formation of mouse aortic plaques,oil red O staining was used to observe lipid accumulation in mouse aorta,and ELISA was used to detect the levels of TG,TC,LDL-C,and HDL-C in serum of mouse.Bioinformatics analyzed the potential binding sites of miR-17-5p with MALAT1 and ABCA1,and dual luciferase reporter gene experiments verified the binding of miR-17-5p with MALAT1 and ABCA1.Results LncRNA MALAT1 was downregulated in the aortic tissue of AS mice,and its overexpression inhibited the formation of atherosclerotic plaques and lipid accumulation in the aortic tissue of AS mice.It also downregulated the levels of TG,TC,and LDL-C in serum of AS mice,and increases the level of HDL-C in serum.miR-17-5p was upregulated in the aortic tissue of AS mice,while ABCA1 was downregulated in the aortic tissue of AS mice.Overexpression of MALAT1 reduced the expression of miR-17-5p in the aortic tissue of AS mice and increased the expression of ABCA1 in the aortic tissue.Overexpression of MALAT1 also reduced the expression of miR-17-5p in peritoneal macrophages of AS mice and upregulated the expression of ABCA1.In addition,miR-17-5p binded to MALAT1 and ABCA1 mRNA.Conclusion Overexpression of MALAT1 inhibits the formation of aortic plaques and lipid accumulation in AS mice,and reduces blood lipid levels.The mechanism may be related to the upregulation of ABCA1 expression by sponge miR-17-5p and inhibition of lipid accumulation in macrophages.
NETL
NSTL
万方数据
