title: MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages.
abstract: Macrophages in atherosclerotic plaques drive inflammatory responses, degrade lipoproteins, and phagocytose dead cells. MicroRNAs (miRs) control the differentiation and activity of macrophages by regulating the signaling of key transcription factors. However, the functional role of macrophage-related miRs in the immune response during atherogenesis is unknown. Here, we report that miR-155 is specifically expressed in atherosclerotic plaques and proinflammatory macrophages, where it was induced by treatment with mildly oxidized LDL (moxLDL) and IFN-γ. Leukocyte-specific Mir155 deficiency reduced plaque size and number of lesional macrophages after partial carotid ligation in atherosclerotic (Apoe-/-) mice. In macrophages stimulated with moxLDL/IFN-γ in vitro, and in lesional macrophages, loss of Mir155 reduced the expression of the chemokine CCL2, which promotes the recruitment of monocytes to atherosclerotic plaques. Additionally, we found that miR-155 directly repressed expression of BCL6, a transcription factor that attenuates proinflammatory NF-κB signaling. Silencing of Bcl6 in mice harboring Mir155-/- macrophages enhanced plaque formation and CCL2 expression. Taken together, these data demonstrated that miR-155 plays a key role in atherogenic programming of macrophages to sustain and enhance vascular inflammation.
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Nazari-Jahantigh
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wei
authors.forename: Heidi
authors.initials: H
authors.lastname: Noels
authors.forename: Shamima
authors.initials: S
authors.lastname: Akhtar
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.forename: Rory R
authors.initials: RR
authors.lastname: Koenen
authors.forename: Kathrin
authors.initials: K
authors.lastname: Heyll
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.forename: Jochen
authors.initials: J
authors.lastname: Grommes
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Andreas
authors.initials: A
authors.lastname: Schober
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051560:Proto-Oncogene Proteins c-bcl-6; D015398:Signal Transduction / Q000235:genetics; D014657:Vasculitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; C490010:Bcl6 protein, mouse; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016328:NF-kappa B; D051560:Proto-Oncogene Proteins c-bcl-6; C099252:oxidized low density lipoprotein; D007371:Interferon-gamma