MicroRNA-590 Inhibits Lipoprotein Lipase Expression and Prevents Atherosclerosis in apoE Knockout Mice.
MicroRNA-590 Inhibits Lipoprotein Lipase Expression and Prevents Atherosclerosis in apoE Knockout Mice.
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MicroRNA-590 抑制 apoE 基因敲除小鼠的脂蛋白脂肪酶表达并预防动脉粥样硬化
DOI：
10.1371/journal.pone.0138788
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tang CK
中科院分区：
文献类型：
--
作者：
He PP;OuYang XP;Li Y;Lv YC;Wang ZB;Yao F;Xie W;Tan YL;Li L;Zhang M;Lan G;Gong D;Cheng HP;Zhong HJ;Liu D;Huang C;Li ZX;Zheng XL;Yin WD;Tang CK
最近的研究表明，miR-590可能在心血管疾病中发挥关键作用。本研究旨在探讨miR-590对载脂蛋白E基因敲除（apoE−/−）小鼠脂蛋白脂酶（LPL）表达和动脉粥样硬化形成的影响及其可能机制。对整个主动脉的正面分析显示，miR-590显著降低了apoE−/−小鼠的主动脉粥样硬化斑块大小和脂质含量。近端主动脉横截面的双重免疫荧光染色显示，miR-590 agomir减少了动脉粥样硬化病变中巨噬细胞中的CD 68和LPL表达。miR-590 agomir下调LPL mRNA和蛋白质表达，分别通过RT-qPCR和蛋白质印迹分析进行分析。结论：miR-590可降低CD 36和清道夫受体A1（SRA 1）mRNA和蛋白的表达。高效液相色谱（HPLC）分析证实，miR-590阿戈米尔治疗降低了apoE−/−小鼠血浆或腹腔巨噬细胞中的脂质水平。ELISA分析显示，miR-590 agomir可降低促炎细胞因子的血浆水平，如肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素-1 β（IL-1β）和白细胞介素-6（IL-6）。相比之下，用miR-590治疗可预防或逆转这些作用。总之，这些结果揭示了miR-590作用的新机制，并可能为开发减少脂质积累和促炎细胞因子分泌的策略提供新的见解。
Recent studies have suggested that miR-590 may play critical roles in cardiovascular disease. This study was designed to determine the effects of miR-590 on lipoprotein lipase (LPL) expression and development of atherosclerosis in apolipoprotein E knockout (apoE−/−) mice and explore the potential mechanisms. En face analysis of the whole aorta revealed that miR-590 significantly decreased aortic atherosclerotic plaque size and lipid content in apoE−/− mice. Double immunofluorescence staining in cross-sections of the proximal aorta showed that miR-590 agomir reduced CD68 and LPL expression in macrophages in atherosclerotic lesions. MiR-590 agomir down-regulated LPL mRNA and protein expression as analyzed by RT-qPCR and western blotting analyses, respectively. Consistently, miR-590 decreased the expression of CD36 and scavenger receptor A1 (SRA1) mRNA and protein. High-performance liquid chromatography (HPLC)analysis confirmed that treatment with miR-590 agomir reduced lipid levels either in plasma orinabdominal cavity macrophages of apoE−/− mice. ELISA analysis showed that miR-590 agomir decreased plasma levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-1β (IL-1β)and interleukin-6 (IL-6). In contrast, treatment with miR-590 antagomir prevented or reversed these effects. Taken together, these results reveal a novel mechanism of miR-590 effects, and may provide new insights into the development of strategies for attenuating lipid accumulation and pro-inflammatory cytokine secretion.