title: MicroRNA-134 actives lipoprotein lipase-mediated lipid accumulation and inflammatory response by targeting angiopoietin-like 4 in THP-1 macrophages.
abstract: Angiopoietin-like 4 (Angptl4), a secreted protein, is an important regulator to irreversibly inhibit lipoprotein lipase (LPL) activity. Macrophage LPL contributes to foam cell formation via a so-called"molecular bridge" between lipoproteins and receptors on cell surface. It has been reported that macrophage ANGPTL4 suppresses LPL activity, foam cell formation and inflammatory gene expression to reduce atherosclerosis development. Recently, some studies demonstrated that microRNA-134 is upregulated in atherosclerotic macrophages. Here we demonstrate that miR-134 directly binds to 3'UTR of ANGPTL4 mRNA to suppression the expression of ANGPTL4. To investigate the potential roles of macrophage miR-134, THP-1 macrophages were transfected with miR-134 mimics or inhibitors. Our results showed that LPL activity and protein were dramatically increased. We also found that miR-134 activated LPL-mediated lipid accumulation. Collectively, our findings indicate that miR-134 may regulate lipid accumulation and proinfiammatory cytokine secretion in macrophages by targeting the ANGPTL4 gene. Our results have also suggested a promising and potential therapeutic target for atherosclerosis.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Tan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Cheng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Gong
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, 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, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China. Electronic address: yysweets@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, Life Science Research Center, University of South China, Hengyang, 421001, Hunan, China. Electronic address: tangchaoke@qq.com.
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000276:immunology*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D050356:Lipid Metabolism / Q000276:immunology*; D008071:Lipoprotein Lipase / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D035683:MicroRNAs / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; C548261:LPL protein, human; D008071:Lipoprotein Lipase
keywords: ANGPTL4; Inflammatory response; Lipid accumulation; MiR-134