Evidence map›Paper›PMID 23867713›Full record

ArticleEpigenetics2013

Role of DNA methyltransferase 1 on the altered eNOS expression in human umbilical endothelium from intrauterine growth restricted fetuses.

Bernardo J Krause, Paula M Costello, Ernesto Muñoz-Urrutia, Karen A Lillycrop, Mark A Hanson, Paola Casanello

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
10.8field-weighted citation impact, top 2% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

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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

6 authors at 4 institutions in 3 countries.

Bernardo J KrauseDivision of Obstetrics and Gynaecology; School of Medicine; Pontificia Universidad Católica de Chile; Santiago, Chile.
Paula M Costello
Ernesto Muñoz-Urrutia
Karen A Lillycrop
Mark A Hanson
Paola Casanello
Pontificia Universidad Católica de Chile · CLInstitute of Developmental Physiology · RUUniversity Hospital Southampton NHS Foundation Trust · GBUniversity of Southampton · GB

Funding

British Heart Foundation
6 · The paper itself

Abstract

Reduced fetal growth associates with endothelial dysfunction and cardiovascular risk in both young and adult offspring and the nitric oxide (NO) system has been implicated in these effects. Epigenetic processes are likely to underlie such effects, but there is to date no evidence that endothelial dysfunction in early life results from epigenetic processes on key genes in the NO system, such as NOS3 (eNOS) and ARG2 (arginase-2). We determined basal DNA methylation status in NOS3 and ARG2 promoters, and DNA methyltransferase 1 (DNMT1) effect on eNOS and arginase-2 expression using human endothelial cells isolated from umbilical arteries (HUAEC) and veins (HUVEC) from control and intrauterine growth restricted (IUGR) fetuses. Compared with cells from control pregnancies, eNOS protein and mRNA levels were increased in HUAEC, but decreased in HUVEC, from IUGR, while arginase-2 levels were increased in IUGR-HUVEC. The NOS3 promoter showed a decrease in DNA methylation at CpG -352 in IUGR-HUAEC, and an increase in IUGR-HUVEC, when compared with control cells. Methylation in the hypoxia response element of the NOS3 promoter was increased in IUGR-HUAEC and decreased in HUVEC. Methylation in the AGR2 promoter in IUGR-HUVEC was decreased in a putative HRE, and without changes in IUGR-HUAEC. Silencing of DNMT1 expression normalized eNOS expression in IUGR endothelial cells, and restored the normal response to hypoxia in HUVEC, without effects on arginase-2. This data suggest that eNOS expression in IUGR-derived endothelial cells is programmed by altered DNA methylation, and can be reversed by transient silencing of the DNA methylation machinery.

Indexed as

AdultArginaseBase SequenceBinding SitesCell HypoxiaCells, CulturedCpG IslandsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationEndothelial CellsEpigenesis, GeneticFemaleFetal Growth RetardationFetusGene Expression Regulation, DevelopmentalARG2 protein, humanArginaseDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNMT1 protein, humanNitric Oxide Synthase Type IIINOS3 protein, humanarginase-2DNA methylationeNOSfetal programminghuman endothelial cellsintrauterine growth restrictionNOS3

Identifiers

PMID23867713
PMCPMC3883771
OpenAlexW2039566085

What OpenQuestion holds

Textmetadata
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.