title: The microRNA-342-5p fosters inflammatory macrophage activation through an Akt1- and microRNA-155-dependent pathway during atherosclerosis.
abstract: BACKGROUND
  Atherosclerosis is a chronic inflammatory vascular disease driven by the subendothelial accumulation of macrophages. The mechanism regulating the inflammatory response in macrophages during atherogenesis remains unclear. Because microRNAs (miRNAs) play a crucial role in cellular signaling by posttranscriptional regulation of gene expression, we studied the miRNA expression profiles during the progression of atherosclerosis.
  
  
  RESULTS
  Using an miRNA real-time polymerase chain reaction array, we found that macrophage-derived miR-342-5p and miR-155 are selectively upregulated in early atherosclerotic lesions in Apoe(-/-) mice. miR-342-5p directly targets Akt1 through its 3'-untranslated region. Akt1 suppression by miR-342-5p induces proinflammatory mediators such as Nos2 and II6 in macrophages via the upregulation of miR-155. The local application of an miR-342-5p antagomir inhibits the development of atherosclerosis in partially ligated carotid arteries. In atherosclerotic lesions, the miR-342-5p antagomir upregulated Akt1 expression and suppressed the expression of miR-155 and Nos2. This reduced Nos2 expression was associated with a diminished generation of nitrotyrosine in the plaques. Furthermore, systemic treatment with an inhibitor of miR-342-5p reduced the progression of atherosclerosis in the aorta of Apoe(-/-) mice.
  
  
  CONCLUSIONS
  Macrophage-derived miR-342-5p promotes atherosclerosis and enhances the inflammatory stimulation of macrophages by suppressing the Akt1-mediated inhibition of miR-155 expression. Therefore, targeting miR-342-5p may offer a promising strategy to treat atherosclerotic vascular disease.
authors.affiliation: Experimental Vascular Medicine, Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 9, 80336 Munich, Germany.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wei
authors.forename: Maliheh
authors.initials: M
authors.lastname: Nazari-Jahantigh
authors.forename: Lily
authors.initials: L
authors.lastname: Chan
authors.forename: Mengyu
authors.initials: M
authors.lastname: Zhu
authors.forename: Kathrin
authors.initials: K
authors.lastname: Heyll
authors.forename: Judit
authors.initials: J
authors.lastname: Corbalán-Campos
authors.forename: Petra
authors.initials: P
authors.lastname: Hartmann
authors.forename: Anna
authors.initials: A
authors.lastname: Thiemann
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Andreas
authors.initials: A
authors.lastname: Schober
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000096:biosynthesis / Q000235:genetics; D016893:Carotid Stenosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D009841:Oligonucleotides / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D016372:RNA, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation; D014657:Vasculitis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C581863:Mirn342 microRNA, mouse; D009841:Oligonucleotides; D016372:RNA, Antisense; C477371:locked nucleic acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; C498219:Bmpr2 protein, mouse; D052006:Bone Morphogenetic Protein Receptors, Type II; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases