title: MicroRNA-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting lipoprotein lipase gene in human THP-1 macrophages.
abstract: 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.
  
  
  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.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; School of Nursing, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: He
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; Department of Physiology, The Neuroscience Institute, Medical College, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Ouyang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tang
authors.affiliation: School of Nursing, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liao
authors.affiliation: Pharmacy and Biological Science College, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Zong-Bao
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lv
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Tian
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Zhao
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Yu Lin
authors.initials: YL
authors.lastname: Tang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Wu-Jun
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China; Pharmacy and Biological Science College, University of South China, Hengyang, Hunan 421001, China. Electronic address: wdy20042004@126.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Yin
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China. Electronic address: tangchaoke@qq.com.
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008055:Lipids / Q000032:analysis*; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D008077:Lipoproteins, LDL; C568221:MIRN590 microRNA, human; D035683:MicroRNAs; C099252:oxidized low density lipoprotein; D008071:Lipoprotein Lipase
keywords: Atherosclerosis; Human THP-1 macrophages; LPL; MiR-590