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首页> 外文期刊>Circulation journal >MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice
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MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice

机译：MicroRNA-182通过靶向载脂蛋白E基因敲除小鼠中的组蛋白去乙酰化酶9促进脂蛋白脂肪酶的表达和动脉粥样硬化的形成。

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Background: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis. Methods?and?Results: Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 ( HDAC9 ) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targeting HDAC9 in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson’s trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. Conclusions: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targeting HDAC9 , leading to an acceleration of atherogenesis in ApoE-KO mice.
机译：背景：在巨噬细胞中表达的脂蛋白脂肪酶（LPL）在促进动脉粥样硬化或动脉粥样硬化的发展中起着重要作用。 MicroRNA-182（miR-182）参与脂质代谢和炎症的调节。但是，尚不清楚miR-182如何调节LPL和动脉粥样硬化。方法和结果：使用生物信息学分析和双重荧光素酶报告基因分析，我们确定了组蛋白脱乙酰基酶9（HDAC9）是miR-182的靶基因。此外，miR-182通过直接靶向THP-1巨噬细胞中的HDAC9来上调LPL表达。苏木精-曙红（H＆E），油红O和Masson的三色染色表明，用miR-182治疗的载脂蛋白E（ApoE）敲除（KO）小鼠表现出更严重的动脉粥样硬化斑块。用miR-182处理可增加ApoE-KO小鼠动脉粥样硬化病变中CD68和LPL的表达，这在主动脉窦中进行了双重免疫荧光染色。实时定量聚合酶链反应和蛋白质印迹分析证实了miR-182诱导的ApoE-KO小鼠LPL表达的增加。使用miR-182进行治疗还增加了ApoE-KO小鼠的促炎细胞因子和脂质的血浆浓度。结论：本研究的结果表明，miR-182可能通过靶向HDAC9来上调LPL表达，促进动脉粥样硬化病变中的脂质蓄积并增加促炎细胞因子的分泌，从而导致ApoE-KO小鼠动脉粥样硬化的加速。

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