Evidence map›Paper›PMID 31326400›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

The Role of MicroRNA-21 in Venous Neointimal Hyperplasia: Implications for Targeting miR-21 for VNH Treatment.

Sreenivasulu Kilari, Chuanqi Cai, Chenglei Zhao, Amit Sharma, Ekaterina Chernogubova, Michael Simeon, Chin-Cheng Wu, Hsiang-Lin Song, Lars Maegdefessel, Sanjay Misra

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. Article
  8. Exosomes in arteriovenous fistula stenosis.Frontiers in cell and developmental biology · 2025
    Review
  9. Article
  10. The rodent models of arteriovenous fistula.Frontiers in cardiovascular medicine · 2024
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 4 countries.

Sreenivasulu KilariVascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Chuanqi CaiVascular 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.
Chenglei ZhaoVascular 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.
Amit SharmaVascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Ekaterina ChernogubovaMolecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Michael SimeonVascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Chin-Cheng WuCardiovascular Center, National Taiwan University Hospital, Hsinchu Branch, Taiwan.
Hsiang-Lin SongPathology Department, National Taiwan University Hospital, Hsinchu Branch, Taiwan.
Lars MaegdefesselMolecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
Sanjay MisraVascular 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.
Mayo Clinic in Arizona · USKarolinska Institutet · SENational Taiwan University Hospital · TWSecond Xiangya Hospital of Central South University · CN

Funding

The Role of Hypoxia In Venous Neointimal Hyperplasia In Hemodialysis GraftsR01HL098967 · NHLBI · MAYO CLINIC ROCHESTER · PI Sanjay Misra · 2010 to 2026
$10.4M
Regulatory gene-chemokine networks in the formation of hemodialysis AVF stenosisR01DK107870 · NIDDK · MAYO CLINIC ROCHESTER · PI KUMAR, RAJIV, MISRA, SANJAY · 2017 to 2019
$716k
Regulatory gene-chemokine networks in the formation of hemodialysis AVF stenosisR56DK107870 · NIDDK · MAYO CLINIC ROCHESTER · PI KUMAR, RAJIV, MISRA, SANJAY · 2020 to 2020
$103k
NHLBI NIH HHS R01 HL098967NIDDK NIH HHS R01 DK107870NIDDK NIH HHS R56 DK107870
6 · The paper itself

Abstract

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 Tgfβ1, 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-1α) 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 Tgfβ-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.

Indexed as

AnimalsApoptosisArteriovenous FistulaBiomarkersCell DifferentiationCell ProliferationDisease Models, AnimalFibroblastsFibrosisGene ExpressionGene Knockdown TechniquesHumansHyperplasiaHypoxiaImmunohistochemistryLentivirusBiomarkersMicroRNAsMIRN21 microRNA, humanRNA, Small Interferinganimal modelsarteriovenous fistulachronic kidney diseasemiR-21TGF-βvascular remodeling

Identifiers

PMID31326400
PMCPMC6731518
OpenAlexW2954429932

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.