LncRNA MALAT1介导miR-17-5p/ABCA1轴抑制动脉粥样硬化发展  

LncRNA MALAT1 mediates miR-17-5p/ABCA1 axis to inhibit the development of atherosclerosis

作　　者：陶斯阳 谭力力[1] TAO Si-yang;TAN Li-li(Department of Cardiology,The Second Affiliated Hospital of Shenyang Medical College,Shenyang 110002,China)

机构地区：[1]沈阳医学院附属第二医院皇姑院区心一科,辽宁沈阳110002

出　　处：《解剖科学进展》2024年第3期321-324,328,共5页Progress of Anatomical Sciences

基　　金：沈阳医学院科技基金(20201017)。

摘　　要：目的探究过表达lncRNA MALAT1对动脉粥样硬化小鼠动脉斑块形成和脂质蓄积以及血脂水平的影响,并进一步探究其介导的miR-17-5p/ABCA1轴在其中发挥的作用。方法将MALAT1过表达慢病毒尾静脉注射AS小鼠,分别采用RT-qPCR和Western blot方法检测小鼠主动脉和腹腔巨噬细胞中MALAT1、miR-17-5p和ABCA1表达情况;HE染色观察小鼠主动脉斑块形成;油红O染色观察小鼠主动脉脂质蓄积;ELISA方法检测小鼠血清中TG、TC、LDL-C和HDL-C水平。生物信息学分析miR-17-5p与MALAT1和ABCA1的潜在结合位点,双荧光素酶报告基因实验验证miR-17-5p与MALAT1和ABCA1结合。结果LncRNA MALAT1在AS小鼠主动脉组织中表达下调,其过表达抑制AS小鼠主动脉组织斑块的形成和脂质的蓄积,下调AS小鼠血清中TG、TC和LDL-C水平,增加血清中HDL-C水平。miR-17-5p在AS小鼠主动脉组织中表达上调,而ABCA1在AS小鼠主动脉组织中表达下调;过表达MALAT1降低AS小鼠主动脉组织中miR-17-5p表达,增加主动脉组织中ABCA1表达;过表达MALAT1还降低了AS小鼠腹腔巨噬细胞中miR-17-5p表达并上调ABCA1表达。此外,miR-17-5p与MALAT1和ABCA1 mRNA结合。结论过表达MALAT1抑制AS小鼠主动脉组织斑块的形成和脂质的蓄积并降低小鼠血脂水平,其机制可能与其海绵化miR-17-5p上调ABCA1表达并抑制巨噬细胞中的脂质积聚有关。Objective To explore the effects of overexpression of lncRNA 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 ABCAl 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.

关 键 词：LncRNA MALAT1 动脉粥样硬化 miR-17-5p ABCA1 巨噬细胞 

分 类 号：R543.5[医药卫生—心血管疾病]