title: miRNA-27b modulates endothelial cell angiogenesis by directly targeting Naa15 in atherogenesis.
abstract: The CCL20/CCR6 axis has been shown to play a vital role in the pathogenesis of atherosclerosis (AS). However, the regulatory mechanism remains unclear. Here, we studied the miRNA-mediated epigenetic regulation of the CCL20/CCR6 axis in atherogenesis.
  
  
  
  CCR6+/+ApoE-/- and CCR6-/-ApoE-/- mice were fed a high-fat diet for 24 weeks. Plaque size was evaluated via ultrasound biomicroscope and hematoxylin and eosin. Protein expression were measured by Western blotting or immunofluorescence/immunohistochemistry or ELISA, and gene mRNA levels were detected by RT-PCR. Seven hundred and sixty miRNAs were screened via miRNA profiling. miRNA-27b target genes were predicted using software and verified with a dual luciferase reporter assay. The tube formation of mouse aortic endothelial cells (MAECs) was performed on Matrigel.
  
  
  
  In contrast to wild-type ApoE-/- mice, CCR6 deficiency led to a significantly decreased plaque size, CD31, CCR6, CCL20 expression and number of CCL20+macrophages in atherosclerotic plaques. Stimulation of mouse primary peritoneal macrophages (MPPMs) resulted in increased IL-23 release. miRNA-27b was the most highly expressed (5.19-fold increase) miRNA among the 760 miRNAs screened in the vessel. Naa15 was verified as miRNA-27b target gene, which was diminished in the plaques. Transfection of siRNA Naa15 or miRNA-27b mimic into MAECs caused an increase tube formation.
  
  
  
  CCR6 deletion effectively ameliorates atherosclerosis progression by reducing macrophage accumulation, resulting in reduced secretion of CCL20 and IL-23. Mechanistically, the decreased miRNA-27b regulates the activity of the CCL20/CCR6 axis by targeting Naa15, and promotes plaque stability in atherosclerosis.
authors.affiliation: The State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Key Laboratory of Stem Cell Biology and Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: liqun@sibs.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Qun
authors.affiliation: The State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wenda
authors.affiliation: Key Laboratory of Stem Cell Biology and Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Weihong
authors.affiliation: Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 20001, China.
authors.forename: Ma
authors.initials: M
authors.lastname: Jianyang
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Wei
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Lou
authors.initials: L
authors.lastname: Fangzhou
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhenyao
authors.affiliation: The State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Key Laboratory of Stem Cell Biology and Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: gaopingjin@sibs.ac.cn.
authors.forename: Gao
authors.initials: G
authors.lastname: Pingjin
mesh_terms: D000818:Animals; D050197:Atherosclerosis; D042783:Endothelial Cells / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D035683:MicroRNAs / Q000378:metabolism*; D063209:N-Terminal Acetyltransferase A / Q000097:blood*; D063213:N-Terminal Acetyltransferase E / Q000097:blood*; D018919:Neovascularization, Physiologic
chemical_list: D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; C427761:Naa15 protein, mouse; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E
keywords: Atherosclerosis; CCR6; Naa15; Tube formation; miRNA-27b