title: MiR-146a inhibits oxidized low-density lipoprotein-induced lipid accumulation and inflammatory response via targeting toll-like receptor 4.
abstract: Atherosclerosis is an inflammatory process due to oxidized low-density lipoprotein (oxLDL) accumulation in macrophages. We investigated the involvement of microRNAs in oxLDL accumulation and inflammatory response in macrophages. The expression of miR-146a decreases under oxLDL stimulation. MiR-146a significantly reduces intracellular LDL cholesterol content and secretion of interleukin 6, interleukin 8, chemokine (C-C motif) ligand 2 and matrix metallopeptidase 9. Toll-like receptor 4 (TLR4) is a relevant target of miR-146a, and miR-146a inhibits the activation of TLR4-dependent intracellular signaling pathways involved in cytoskeleton rearrangement, lipid uptake, and inflammatory cytokine secretion. These results indicate that miR-146a contributes to the regulation of both oxLDL accumulation and inflammatory response by negatively regulating TLR4 and thereby inhibiting the activation of TLR4-dependent signaling pathways. Over-expression of miR-146a may be useful in the prevention and treatment of atherosclerosis.
authors.affiliation: Department of Cardiology, Rui Jin Hospital, Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Yu Song
authors.initials: YS
authors.lastname: He
authors.forename: Xiao Qun
authors.initials: XQ
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Qiu Jing
authors.initials: QJ
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Shen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008078:Cholesterol, LDL; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008077:Lipoproteins, LDL; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein; D020780:Matrix Metalloproteinase 9