PMID- 27755984
OWN - NLM
STAT- MEDLINE
DCOM- 20171220
LR  - 20191210
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 254
DP  - 2016 Nov
TI  - miRNA-27b modulates endothelial cell angiogenesis by directly targeting Naa15 in 
      atherogenesis.
PG  - 184-192
LID - S0021-9150(16)31410-1 [pii]
LID - 10.1016/j.atherosclerosis.2016.10.007 [doi]
AB  - BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Qun, Li
AU  - Qun L
AD  - 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.
FAU - Wenda, Xi
AU  - Wenda X
AD  - 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.
FAU - Weihong, Sun
AU  - Weihong S
AD  - 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.
FAU - Jianyang, Ma
AU  - Jianyang M
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong 
      University, School of Medicine, Shanghai, 20001, China.
FAU - Wei, Cai
AU  - Wei C
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, 200025, China.
FAU - Fangzhou, Lou
AU  - Fangzhou L
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, 200025, China.
FAU - Zhenyao, Xu
AU  - Zhenyao X
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, 200025, China.
FAU - Pingjin, Gao
AU  - Pingjin G
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20161008
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn27 microRNA, mouse)
RN  - 0 (Naa15 protein, mouse)
RN  - EC 2.3.1.254 (N-Terminal Acetyltransferase A)
RN  - EC 2.3.1.258 (N-Terminal Acetyltransferase E)
SB  - IM
MH  - Animals
MH  - Atherosclerosis
MH  - Endothelial Cells/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout, ApoE
MH  - MicroRNAs/*metabolism
MH  - N-Terminal Acetyltransferase A/*blood
MH  - N-Terminal Acetyltransferase E/*blood
MH  - *Neovascularization, Physiologic
OTO - NOTNLM
OT  - Atherosclerosis
OT  - CCR6
OT  - Naa15
OT  - Tube formation
OT  - miRNA-27b
EDAT- 2016/10/19 06:00
MHDA- 2017/12/21 06:00
CRDT- 2016/11/06 06:00
PHST- 2016/05/11 00:00 [received]
PHST- 2016/09/06 00:00 [revised]
PHST- 2016/10/04 00:00 [accepted]
PHST- 2016/11/06 06:00 [entrez]
PHST- 2016/10/19 06:00 [pubmed]
PHST- 2017/12/21 06:00 [medline]
AID - S0021-9150(16)31410-1 [pii]
AID - 10.1016/j.atherosclerosis.2016.10.007 [doi]
PST - ppublish
SO  - Atherosclerosis. 2016 Nov;254:184-192. doi: 
      10.1016/j.atherosclerosis.2016.10.007. Epub 2016 Oct 8.