Evidence map›Paper›PMID 33256815›Full record

Observational studyClinical epigenetics2020

Developmental programming in human umbilical cord vein endothelial cells following fetal growth restriction.

Fieke Terstappen, Jorg J A Calis, Nina D Paauw, Jaap A Joles, Bas B van Rijn, Michal Mokry, Torsten Plösch, A Titia Lely

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Clinical epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.9field-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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. The Update of Fetal Growth Restriction Associated with Biomarkers.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2022
    Review
  12. 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

8 authors at 3 institutions in 1 country.

Fieke TerstappenDivision Woman and Baby, Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Postbus 85090, 3508 AB, Utrecht, The Netherlands. F.Terstappen@umcutrecht.nl.ORCID 0000-0002-6587-1320
Jorg J A CalisDepartment of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Nina D PaauwDivision Woman and Baby, Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Postbus 85090, 3508 AB, Utrecht, The Netherlands.
Jaap A JolesDepartment of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
Bas B van RijnDepartment of Obstetrics and Fetal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Michal MokryDepartment of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Torsten PlöschDepartment of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
A Titia LelyDivision Woman and Baby, Department of Obstetrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Postbus 85090, 3508 AB, Utrecht, The Netherlands.
University Medical Center Utrecht · NLErasmus MC · NLUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFetal growth restriction (FGR) is associated with an increased susceptibility for various noncommunicable diseases in adulthood, including cardiovascular and renal disease. During FGR, reduced uteroplacental blood flow, oxygen and nutrient supply to the fetus are hypothesized to detrimentally influence cardiovascular and renal programming. This study examined whether developmental programming profiles, especially related to the cardiovascular and renal system, differ in human umbilical vein endothelial cells (HUVECs) collected from pregnancies complicated by placental insufficiency-induced FGR compared to normal growth pregnancies. Our approach, involving transcriptomic profiling by RNA-sequencing and gene set enrichment analysis focused on cardiovascular and renal gene sets and targeted DNA methylation assays, contributes to the identification of targets underlying long-term cardiovascular and renal diseases.

resultsGene set enrichment analysis showed several downregulated gene sets, most of them involved in immune or inflammatory pathways or cell cycle pathways. seven of the 22 significantly upregulated gene sets related to kidney development and four gene sets involved with cardiovascular health and function were downregulated in FGR (n = 11) versus control (n = 8). Transcriptomic profiling by RNA-sequencing revealed downregulated expression of LGALS1, FPR3 and NRM and upregulation of lincRNA RP5-855F14.1 in FGR compared to controls. DNA methylation was similar for LGALS1 between study groups, but relative hypomethylation of FPR3 and hypermethylation of NRM were present in FGR, especially in male offspring. Absolute differences in methylation were, however, small.

conclusionThis study showed upregulation of gene sets related to renal development in HUVECs collected from pregnancies complicated by FGR compared to control donors. The differentially expressed gene sets related to cardiovascular function and health might be in line with the downregulated expression of NRM and upregulated expression of lincRNA RP5-855F14.1 in FGR samples; NRM is involved in cardiac remodeling, and lincRNAs are correlated with cardiovascular diseases. Future studies should elucidate whether the downregulated LGALS1 and FPR3 expressions in FGR are angiogenesis-modulating regulators leading to placental insufficiency-induced FGR or whether the expression of these genes can be used as a biomarker for increased cardiovascular risk. Altered DNA methylation might partly underlie FPR3 and NRM differential gene expression differences in a sex-dependent manner.

Indexed as

AdultCardiovascular DiseasesCase-Control StudiesCpG IslandsDNA MethylationEpigenomicsFemaleFetal Growth RetardationFetusGalectin 1Gene Expression ProfilingGene Expression RegulationHumansHuman Umbilical Vein Endothelial CellsKidney DiseasesMaleFPR3 protein, humanGalectin 1LGALS1 protein, humanMembrane ProteinsNuclear ProteinsnurimReceptors, Formyl PeptideRNA, Long NoncodingDevelopmental programmingDNA methylationEpigeneticsFetal growth restrictionFPR3Gene set enrichment analysisHuman umbilical cord vein endothelial cellsLGALS1NRMRNA-sequencingSex differences

Identifiers

PMID33256815
PMCPMC7708922
OpenAlexW3108054816

What OpenQuestion holds

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LicenceCC BY
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.