Evidence map›Paper›PMID 30819028›Full record

ArticleJournal of the American Heart Association2019

Influence of 2-Methoxyestradiol and Sex on Hypoxia-Induced Pulmonary Hypertension and Hypoxia-Inducible Factor-1-α.

Craig K Docherty, Margaret Nilsen, Margaret R MacLean

Open access · goldAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Heart Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

37 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Observational
  5. Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025
    Review
  6. Nobiletin: a potential erythropoietin receptor activator protects renal cells against hypoxia.Apoptosis : an international journal on programmed cell death · 2025
    Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. [Protective effects of 2-methoxyestradiol against hypoxic pulmonary hypertension in neonatal rats].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Sex and gender in pulmonary arterial hypertension.European respiratory review : an official journal of the European Respiratory Society · 2021
    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

3 authors at 1 institution in 1 country.

Craig K Docherty1 Research Institute of Cardiovascular and Medical Sciences College of Medical, Veterinary and Life Sciences University of Glasgow United Kingdom.
Margaret Nilsen1 Research Institute of Cardiovascular and Medical Sciences College of Medical, Veterinary and Life Sciences University of Glasgow United Kingdom.
Margaret R MacLean1 Research Institute of Cardiovascular and Medical Sciences College of Medical, Veterinary and Life Sciences University of Glasgow United Kingdom.
University of Glasgow · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background Women are at greater risk of developing pulmonary arterial hypertension, with estrogen and its downstream metabolites playing a potential role in the pathogenesis of the disease. Hypoxia-inducible factor-1-α (HIF 1α) is a pro-proliferative mediator and may be involved in the development of human pulmonary arterial hypertension . The estrogen metabolite 2-methoxyestradiol (2 ME 2) has antiproliferative properties and is also an inhibitor of HIF 1α. Here, we examine sex differences in  HIF 1α signaling in the rat and human pulmonary circulation and determine if 2 ME 2 can inhibit HIF 1α in vivo and in vitro. Methods and Results HIF 1α signaling was assessed in male and female distal human pulmonary artery smooth muscle cells ( hPASMC s), and the effects of 2 ME 2 were also studied in female hPASMC s. The in vivo effects of 2 ME 2 in the chronic hypoxic rat (male and female) model of pulmonary hypertension were also determined. Basal HIF 1α protein expression was higher in female hPASMC s compared with male. Both factor-inhibiting HIF and prolyl hydroxylase-2 (hydroxylates HIF leading to proteosomal degradation) protein levels were significantly lower in female hPASMC s when compared with males. In vivo, 2 ME 2 ablated hypoxia-induced pulmonary hypertension in male and female rats while decreasing protein expression of HIF 1α. 2 ME 2 reduced proliferation in hPASMC s and reduced basal protein expression of HIF 1α. Furthermore, 2 ME 2 caused apoptosis and significant disruption to the microtubule network. Conclusions Higher basal HIF 1α in female hPASMC s may increase susceptibility to developing pulmonary arterial hypertension . These data also demonstrate that the antiproliferative and therapeutic effects of 2 ME 2 in pulmonary hypertension may involve inhibition of HIF 1α and/or microtubular disruption in PASMC s.

Indexed as

2-MethoxyestradiolAnimalsApoptosisCell ProliferationCells, CulturedCytoskeletonDisease Models, AnimalFemaleHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitMaleMuscle, Smooth, VascularMyocytes, Smooth MusclePulmonary Arterial HypertensionPulmonary Artery2-MethoxyestradiolHIF1A protein, humanHif1a protein, mouseHypoxia-Inducible Factor 1, alpha Subunit2‐methoxyestradiolHIF1αpulmonary arterial hypertensionpulmonary hypertensionpulmonary vascular changessex hormonessmooth muscle cell

Identifiers

PMID30819028
PMCPMC6474940
OpenAlexW2915165159

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.