title: MicroRNA-155 deficiency results in decreased macrophage inflammation and attenuated atherogenesis in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  microRNA-155 (miR155) plays a critical role in immunity and macrophage inflammation. We aim to investigate the role of miR155 in atherogenesis.
  
  
  RESULTS
  Quantitative real-time polymerase chain reaction showed that miR155 was expressed in mouse and human atherosclerotic lesions. miR155 expression in macrophages was correlated positively with proinflammatory cytokine expression. Lentivirus-mediated overexpression of miR155 in macrophages enhanced their inflammatory response to lipopolysaccharide through targeting suppressor of cytokine signaling-1 and impaired cholesterol efflux from acetylated low-density lipoprotein-loaded macrophages, whereas deficiency of miR155 blunted macrophage inflammatory responses and enhanced cholesterol efflux possibly via enhancing lipid loading-induced macrophage autophagy. We next examined the atherogenesis in apolipoprotein E-deficient (apoE(-/-)) and miR155(-/-)/apoE(-/-) (double knockout) mice fed a Western diet. Compared with apoE(-/-) mice, the double knockout mice developed less atherosclerosis lesion in aortic root, with reduced neutral lipid content and macrophages. Flow cytometric analysis showed that there were increased number of regulatory T cells and reduced numbers of Th17 cells and CD11b+/Ly6C(high) cells in the spleen of double knockout mice. Peritoneal macrophages from the double knockout mice had significantly reduced proinflammatory cytokine expression and secretion both in the absence and presence of lipopolysaccharide stimulation. To determine whether miR155 in leukocytes contributes to atherosclerosis, we performed a bone marrow transplantation study. Deficiency of miR155 in bone marrow-derived cells suppressed atherogenesis in apoE(-/-) mice, demonstrating that hematopoietic cell-derived miR155 plays a critical role.
  
  
  CONCLUSIONS
  miR155 deficiency attenuates atherogenesis in apoE(-/-) mice by reducing inflammatory responses of macrophages, enhancing macrophage cholesterol efflux and resulting in an antiatherogenic leukocyte profile. Targeting miR155 may be a promising strategy to halt atherogenesis.
authors: From the Department of Biochemistry and Molecular Biology, School of Basic Medicine, Wuhan University, Wuhan, PR China (F.D.); the Department of Cell Biology and Anatomy (F.D., F.Y., Y.W., Y.H, H.L., D.F.) and the Department of Pathology, Microbiology, and Immunology (K.C.), University of South Carolina School of Medicine, Columbia; Department of Nutrition and Food Hygiene, the Fourth Military Medical University, Xi'an, Shaanxi, PR China (F.Y.); and Department of Basic Medical Science, School of Medicine, Shock/Trauma Research Center, University of Missouri, Kansas City (M.F.).
authors: Fen
authors: F
authors: Du
authors: Fang
authors: F
authors: Yu
authors: Yuzhen
authors: Y
authors: Wang
authors: Yvonne
authors: Y
authors: Hui
authors: Kevin
authors: K
authors: Carnevale
authors: Mingui
authors: M
authors: Fu
authors: Hong
authors: H
authors: Lu
authors: Daping
authors: D
authors: Fan
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014162:Transfection
chemical_list: D000950:Antigens, Ly; D001057:Apolipoproteins E; D015415:Biomarkers; D039481:CD11b Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C494192:Ly-6C antigen, mouse; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D002784:Cholesterol
keywords: atherosclerosis; inflammation; macrophages; microRNA