Evidence map›Paper›PMID 25979369›Full record

ReviewThe international journal of biochemistry & cell biology2015

The role of epigenetics in the endothelial cell shear stress response and atherosclerosis.

Jessilyn Dunn, Rachel Simmons, Salim Thabet, Hanjoong Jo

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The international journal of biochemistry & cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

31 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Mechanisms of endothelial flow sensing.Nature cardiovascular research · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. METTL3-dependent NProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Article
  16. Carotid artery plaque composition and distribution: near-infrared spectroscopy and intravascular ultrasound analysis.European heart journal supplements : journal of the European Society of Cardiology · 2020
    Article
  17. Early Programming of Adult Systemic Essential Hypertension.International journal of molecular sciences · 2020
    Review
  18. Review
  19. Review
  20. Review
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

4 authors at 1 institution in 1 country.

Jessilyn DunnWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA.
Rachel SimmonsWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA.
Salim ThabetDivision of Cardiology, Georgia Institute of Technology and Emory University, USA.
Hanjoong JoWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, USA; Division of Cardiology, Georgia Institute of Technology and Emory University, USA. Electronic address: hjo@bme.gatech.edu.
Georgia Institute of Technology · US

Funding

T cell triggering events and hypertensionP01HL095070 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2009 to 2019
$20.5M
Shear stress, endothelial miRNAs, and AV calcificationR01HL119798 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG, YOGANATHAN, AJIT P · 2013 to 2022
$4.7M
Metabolomics of subclinical and clinical cardiovascular diseaseP20HL113451 · NHLBI · EMORY UNIVERSITY · PI JONES, DEAN PAUL · 2012 to 2016
$4.3M
Image-based analysis of miRNA deliveryR01HL124879 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FERRARA, KATHERINE W, JO, HANJOONG · 2014 to 2017
$3.1M
Shear Stress, BMP and Aortic Valve InflammationR01HL087012 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2007 to 2010
$1.9M
NHLBI NIH HHS P01 HL095070NHLBI NIH HHS P20 HL113451NHLBI NIH HHS R01 HL087012NHLBI NIH HHS R01 HL119798NHLBI NIH HHS R01 HL124879
6 · The paper itself

Abstract

Currently in the field of vascular biology, the role of epigenetics in endothelial cell biology and vascular disease has attracted more in-depth study. Using both in vitro and in vivo models of blood flow, investigators have recently begun to reveal the underlying epigenetic regulation of endothelial gene expression. Recently, our group, along with two other independent groups, have demonstrated that blood flow controls endothelial gene expression by DNA methyltransferases (DNMT1 and 3A). Disturbed flow (d-flow), characterized by low and oscillating shear stress (OS), is pro-atherogenic and induces expression of DNMT1 both in vivo and in vitro. D-flow regulates genome-wide DNA methylation patterns in a DNMT-dependent manner. The DNMT inhibitor 5-Aza-2'deoxycytidine (5Aza) or DNMT1 siRNA reduces OS-induced endothelial inflammation. Moreover, 5Aza inhibits the development of atherosclerosis in ApoE(-/-) mice. Through a systems biological analysis of genome-wide DNA methylation patterns and gene expression data, we found 11 mechanosensitive genes which were suppressed by d-flow in vivo, experienced hypermethylation in their promoter region in response to d-flow, and were rescued by 5Aza treatment. Interestingly, among these mechanosensitive genes, the two transcription factors HoxA5 and Klf3 contain cAMP-response-elements (CRE), which may indicate that methylation of CRE sites could serve as a mechanosensitive master switch in gene expression. These findings provide new insight into the mechanism by which flow controls epigenetic DNA methylation patterns, which in turn alters endothelial gene expression, regulates vascular biology, and induces atherosclerosis. These novel findings have broad implications for understanding the biochemical mechanisms of atherogenesis and provide a basis for identifying potential therapeutic targets for atherosclerosis. This article is part of a Directed Issue entitled: Epigenetics dynamics in development and disease.

Indexed as

Epigenesis, GeneticAnimalsApolipoproteins EAtherosclerosisAzacitidineDecitabineDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEndothelial CellsHemodynamicsHomeodomain ProteinsHumansKruppel-Like Transcription FactorsMechanotransduction, CellularApolipoproteins EAzacitidineDecitabineDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT1 protein, humanDnmt1 protein, mouseDNMT3A protein, humanHomeodomain ProteinsHOXA5 protein, humanKLF3 protein, humanKruppel-Like Transcription FactorsRNA, Small InterferingAtherosclerosisDNMTEndothelial functionEpigenetic DNA methylationFlowGene expressionShear stress

Identifiers

PMID25979369
PMCPMC4592147
OpenAlexW1894889351

What OpenQuestion holds

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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.