Evidence map›Paper›PMID 25987666›Full record

ArticleHypertension (Dallas, Tex. : 1979)2015

Hypoxia Represses ER-α Expression and Inhibits Estrogen-Induced Regulation of Ca2+-Activated K+ Channel Activity and Myogenic Tone in Ovine Uterine Arteries: Causal Role of DNA Methylation.

Man Chen, Daliao Xiao, Xiang-Qun Hu, Chiranjib Dasgupta, Shumei Yang, Lubo Zhang

Open access · bronzeAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

20 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. The uteroplacental circulation at high altitude: adaptation and maladaptation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  3. Review
  4. Article
  5. CaInternational journal of molecular sciences · 2023
    Review
  6. Review
  7. Estrogen-Induced Uterine Vasodilation in Pregnancy and Preeclampsia.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2022
    Review
  8. Review
  9. Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy.International journal of molecular sciences · 2020
    Review
  10. Review
  11. Genome-wide DNA methylation encodes cardiac transcriptional reprogramming in human ischemic heart failure.Laboratory investigation; a journal of technical methods and pathology · 2019
    Article
  12. Effect of Oxidative Stress on the Estrogen-NOS-NO-KOxidative medicine and cellular longevity · 2019
    Review
  13. Epigenetic Mechanisms and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018
    Review
  14. Article
  15. Review
  16. BKHypertension research : official journal of the Japanese Society of Hypertension · 2018
    Article
  17. Article
  18. Pregnancy Reprograms Large-Conductance CaHypertension (Dallas, Tex. : 1979) · 2017
    Article
  19. Article
  20. Article
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 1 institution in 1 country.

Man ChenFrom the Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, CA (M.C., D.X., X-.Q.H., C.D., L.Z.); and Department of Chemistry and Biochemistry, California State University, San Bernardino (S.Y.).
Daliao XiaoFrom the Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, CA (M.C., D.X., X-.Q.H., C.D., L.Z.); and Department of Chemistry and Biochemistry, California State University, San Bernardino (S.Y.).
Xiang-Qun HuFrom the Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, CA (M.C., D.X., X-.Q.H., C.D., L.Z.); and Department of Chemistry and Biochemistry, California State University, San Bernardino (S.Y.).
Chiranjib DasguptaFrom the Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, CA (M.C., D.X., X-.Q.H., C.D., L.Z.); and Department of Chemistry and Biochemistry, California State University, San Bernardino (S.Y.).
Shumei YangFrom the Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, CA (M.C., D.X., X-.Q.H., C.D., L.Z.); and Department of Chemistry and Biochemistry, California State University, San Bernardino (S.Y.).
Lubo ZhangFrom the Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, CA (M.C., D.X., X-.Q.H., C.D., L.Z.); and Department of Chemistry and Biochemistry, California State University, San Bernardino (S.Y.). lzhang@llu.edu.
Loma Linda University · US

Funding

Uterine vascular responses to pregnancy and long term hypoxemiaP01HD031226 · NICHD · LOMA LINDA UNIVERSITY · PI ZHANG, LUBO · 1995 to 2014
$21.4M
Hypoxia and Aberrant Uterine Vascular Adaptation in PregnancyR01HL110125 · NHLBI · LOMA LINDA UNIVERSITY · PI ZHANG, LUBO · 2011 to 2015
$1.8M
Steroid Hormones and Uterine Vascular Adaptation to PregnancyR01HL089012 · NHLBI · LOMA LINDA UNIVERSITY · PI ZHANG, LUBO · 2008 to 2012
$1.8M
Epigenetic mechanisms of uterine vascular adaptation to pregnancy and hypoxiaR01HL128209 · NHLBI · LOMA LINDA UNIVERSITY · PI ZHANG, LUBO · 2015 to 2018
$1.6M
DNA Demethylation and BKca Channel Expression and Function in Uterine ArteriesR21HD083232 · NICHD · LOMA LINDA UNIVERSITY · PI ZHANG, LUBO · 2015 to 2016
$433k
NHLBI NIH HHS HL089012NHLBI NIH HHS HL110125NHLBI NIH HHS R01 HL089012NHLBI NIH HHS R01 HL110125NHLBI NIH HHS R01 HL128209NICHD NIH HHS HD031226NICHD NIH HHS P01 HD031226NICHD NIH HHS R21 HD083232
6 · The paper itself

Abstract

Previous in vivo study demonstrated that chronic hypoxia during gestation was associated with estrogen receptor-α (ER-α) gene repression in ovine uterine arteries. Yet, it remains undetermined whether hypoxia had a direct effect and if DNA methylation played a causal role in hypoxia-mediated ER-α gene repression. Thus, this study tested the hypothesis that prolonged hypoxia has a direct effect and increases promoter methylation resulting in ER-α gene repression and inhibition of estrogen-mediated adaptation of uterine vascular tone. Uterine arteries isolated from nonpregnant and pregnant sheep were treated ex vivo with 21.0% O2 and 10.5% O2 for 48 hours. Hypoxia significantly increased ER-α promoter methylation at both specificity protein-1 and upstream stimulatory factor binding sites, decreased specificity protein-1 and upstream stimulatory factor binding to the promoter, and suppressed ER-α expression in uterine arteries of pregnant animals. Of importance, the effects of hypoxia were blocked by a methylation inhibitor 5-aza-2'-deoxycytidine. In addition, hypoxia abrogated steroid hormone-mediated increase in ER-α expression and inhibited the hormone-induced increase in large-conductance Ca(2+)-activated K(+) channel activity and decrease in myogenic tone in uterine arteries of nonpregnant animals, which were reversed by 5-aza-2'-deoxycytidine. The results provide novel evidence of a direct effect of hypoxia on heightened promoter methylation that plays a causal role in ER-α gene repression and ablation of steroid hormone-mediated adaptation of uterine arterial large conductance Ca(2+)-activated K(+) channel activity and myogenic tone in pregnancy.

Indexed as

DNA MethylationAcetylcysteineAnimalsAzacitidineDecitabineEstradiolEstrogen Receptor alphaFemaleGene Expression RegulationHypoxiaLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsPregnancyPregnancy ComplicationsProgesteronePromoter Regions, GeneticReactive Oxygen SpeciesAcetylcysteineAzacitidineDecitabineEstradiolEstrogen Receptor alphaLarge-Conductance Calcium-Activated Potassium Channel alpha SubunitsProgesteroneReactive Oxygen SpeciesDNA methylationgene expressiongonadal steroid hormonespregnancy

Identifiers

PMID25987666
PMCPMC4465851
OpenAlexW2732707811

What OpenQuestion holds

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LicenceTDM
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.