MicroRNA-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting lipoprotein lipase gene in human THP-1 macrophages.
BACKGROUND
Accumulating evidence suggests that microRNA-590 (miR-590) has protective effects on cardiovascular diseases, but the mechanism is unknown. Interestingly, previous studies from our laboratory and others have shown that macrophage-derived lipoprotein lipase (LPL) might accelerate atherosclerosis by promoting lipid accumulation and inflammatory response. However, the regulation of LPL at the post-transcriptional level by microRNAs has not been fully understood. In this study, we explored whether miR-590 affects the expression of LPL and its potential subsequent effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages.


METHODS AND RESULTS
Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-590 directly inhibited LPL protein and mRNA expression by targeting LPL 3'UTR. LPL Activity Assays showed that miR-590 reduced LPL activity in the culture media. Oil Red O staining and high-performance liquid chromatography assays showed that miR-590 had inhibitory effects on the lipid accumulation in human THP-1 macrophages. We also illustrated that miR-590 alleviated pro-inflammatory cytokine secretion in human THP-1 macrophages as measured by ELISA. With the method of small interfering RNA, we found that LPL siRNA can inhibit the miR-590 inhibitor-induced increase in lipid accumulation and secretion of pro-inflammatory cytokines in oxLDL-treated human THP-1 macrophages.


CONCLUSIONS
MiR-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting LPL gene in human THP-1 macrophages. Therefore, targeting miR-590 may offer a promising strategy to treat atherosclerotic cardiovascular diseases.
['He|Ping-Ping|PP|', 'Ouyang|Xin-Ping|XP|', 'Tang|Yan-Yan|YY|', 'Liao|Li|L|', 'Wang|Zong-Bao|ZB|', 'Lv|Yun-Cheng|YC|', 'Tian|Guo-Ping|GP|', 'Zhao|Guo-Jun|GJ|', 'Huang|Liang|L|', 'Yao|Feng|F|', 'Xie|Wei|W|', 'Tang|Yu Lin|YL|', 'Chen|Wu-Jun|WJ|', 'Zhang|Min|M|', 'Li|Yuan|Y|', 'Wu|Jian-Feng|JF|', 'Peng|Juan|J|', 'Liu|Xiang-Yu|XY|', 'Zheng|Xi-Long|XL|', 'Yin|Wei-Dong|WD|', 'Tang|Chao-Ke|CK|']
D020413:3' Untranslated Regions D001483:Base Sequence D015153:Blotting, Western D045744:Cell Line, Tumor D016207:Cytokines D015870:Gene Expression D057809:HEK293 Cells D006801:Humans D018836:Inflammation Mediators D008055:Lipids D008071:Lipoprotein Lipase D008077:Lipoproteins, LDL D008264:Macrophages D035683:MicroRNAs D034622:RNA Interference D020133:Reverse Transcriptase Polymerase Chain Reaction D012689:Sequence Homology, Nucleic Acid
Human THP-1 macrophages MiR-590 LPL Atherosclerosis