PMID- 31326400
OWN - NLM
STAT- MEDLINE
DCOM- 20200616
LR  - 20211231
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 27
IP  - 9
DP  - 2019 Sep 4
TI  - The Role of MicroRNA-21 in Venous Neointimal Hyperplasia: Implications for 
      Targeting miR-21 for VNH Treatment.
PG  - 1681-1693
LID - S1525-0016(19)30306-5 [pii]
LID - 10.1016/j.ymthe.2019.06.011 [doi]
AB  - The molecular mechanism of hemodialysis access arteriovenous fistula (AVF) 
      failure due to venous neointimal hyperplasia (VNH) is not known. The role of 
      microRNA-21 (miR-21) in VNH associated with AVF failure was investigated by 
      performing in vivo and in vitro experiments. In situ hybridization results 
      revealed that miR-21 expression increased and was associated with fibroblasts in 
      failed AVFs from patients. In a murine AVF model, qRT-PCR gene expression results 
      showed a significant increase in miR-21 and a decrease in miR-21 target genes in 
      graft veins (GVs) compared to contralateral veins in mouse AVF. miR-21 knockdown 
      in GVs was performed using a lentivirus-mediated small hairpin RNA (shRNA), and 
      this improved AVF patency with a decrease in neointima compared to control GVs. 
      Moreover, loss of miR-21 in GVs significantly decreased the Tgfbeta1, Col-Ia, and 
      Col-Iva genes. Immunohistochemistry demonstrated a significant decrease in 
      myofibroblasts and proliferation with an increase in terminal deoxynucleotidyl 
      transferase dUTP nick-end labeling (TUNEL) staining in miR-21-knockdown vessels, 
      along with a decrease in hypoxia-inducible factor-1 alpha (HIF-1alpha) and 
      phospho-SMAD2 (pSMAD-2) and phospho-SMAD3 (pSMAD-3) and an increase in 
      phosphatase and tensin homolog (PTEN) staining. Hypoxic fibroblast knockdown for 
      miR-21 showed a significant decrease in Tgfbeta-1 expression and pSMAD-2 and -3 
      levels and a decrease in myofibroblasts. These results indicate that miR-21 
      upregulation causes VNH formation by fibroblast-to-myofibroblast differentiation.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kilari, Sreenivasulu
AU  - Kilari S
AD  - Vascular and Interventional Radiology Translational Laboratory, Department of 
      Radiology, Mayo Clinic, Rochester, MN, USA.
FAU - Cai, Chuanqi
AU  - Cai C
AD  - Vascular and Interventional Radiology Translational Laboratory, Department of 
      Radiology, Mayo Clinic, Rochester, MN, USA; Department of Vascular Surgery, Union 
      Hospital, Tongji Medical College, Huazhong University of Science and Technology, 
      Wuhan, China.
FAU - Zhao, Chenglei
AU  - Zhao C
AD  - Vascular and Interventional Radiology Translational Laboratory, Department of 
      Radiology, Mayo Clinic, Rochester, MN, USA; Department of Vascular Surgery, The 
      Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
FAU - Sharma, Amit
AU  - Sharma A
AD  - Vascular and Interventional Radiology Translational Laboratory, Department of 
      Radiology, Mayo Clinic, Rochester, MN, USA.
FAU - Chernogubova, Ekaterina
AU  - Chernogubova E
AD  - Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
FAU - Simeon, Michael
AU  - Simeon M
AD  - Vascular and Interventional Radiology Translational Laboratory, Department of 
      Radiology, Mayo Clinic, Rochester, MN, USA.
FAU - Wu, Chin-Cheng
AU  - Wu CC
AD  - Cardiovascular Center, National Taiwan University Hospital, Hsinchu Branch, 
      Taiwan.
FAU - Song, Hsiang-Lin
AU  - Song HL
AD  - Pathology Department, National Taiwan University Hospital, Hsinchu Branch, 
      Taiwan.
FAU - Maegdefessel, Lars
AU  - Maegdefessel L
AD  - Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
FAU - Misra, Sanjay
AU  - Misra S
AD  - Vascular and Interventional Radiology Translational Laboratory, Department of 
      Radiology, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and 
      Molecular Biology, Mayo Clinic, Rochester, MN, USA. Electronic address: 
      misra.sanjay@mayo.edu.
LA  - eng
GR  - R01 DK107870/DK/NIDDK NIH HHS/United States
GR  - R01 HL098967/HL/NHLBI NIH HHS/United States
GR  - R56 DK107870/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190703
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Biomarkers)
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Arteriovenous Fistula/genetics/pathology
MH  - Biomarkers
MH  - Cell Differentiation/genetics
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Fibroblasts/metabolism
MH  - Fibrosis/genetics
MH  - Gene Expression
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Hyperplasia
MH  - Hypoxia/genetics/metabolism
MH  - Immunohistochemistry
MH  - Lentivirus/genetics
MH  - Male
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Myofibroblasts/metabolism
MH  - Neointima/*genetics/*pathology/therapy
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics
MH  - Transduction, Genetic
MH  - Veins/*metabolism/*pathology
PMC - PMC6731518
OTO - NOTNLM
OT  - TGF-beta
OT  - animal models
OT  - arteriovenous fistula
OT  - chronic kidney disease
OT  - miR-21
OT  - vascular remodeling
EDAT- 2019/07/22 06:00
MHDA- 2020/06/17 06:00
PMCR- 2020/09/04
CRDT- 2019/07/22 06:00
PHST- 2018/11/25 00:00 [received]
PHST- 2019/06/12 00:00 [revised]
PHST- 2019/06/19 00:00 [accepted]
PHST- 2019/07/22 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2019/07/22 06:00 [entrez]
PHST- 2020/09/04 00:00 [pmc-release]
AID - S1525-0016(19)30306-5 [pii]
AID - 10.1016/j.ymthe.2019.06.011 [doi]
PST - ppublish
SO  - Mol Ther. 2019 Sep 4;27(9):1681-1693. doi: 10.1016/j.ymthe.2019.06.011. Epub 2019 
      Jul 3.