Evidence map›Paper›PMID 33001586›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2021

Dissecting the Cellular Mechanism of Prostacyclin Analog Iloprost in Reversing Vascular Dysfunction in Scleroderma.

Pei-Suen Tsou, Pamela J Palisoc, Nicholas A Flavahan, Dinesh Khanna

Open access · bronzeAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

23 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Endothelial Dysfunction in Systemic Sclerosis.International journal of molecular sciences · 2023
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  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

4 authors at 2 institutions in 1 country.

Pei-Suen TsouUniversity of Michigan, Ann Arbor.ORCID 0000-0002-7149-9115
Pamela J PalisocUniversity of Michigan, Ann Arbor.
Nicholas A FlavahanJohns Hopkins University School of Medicine, Baltimore, Maryland.
Dinesh KhannaUniversity of Michigan, Ann Arbor.ORCID 0000-0003-1412-4453
University of Michigan · USJohns Hopkins University · US

Funding

Michigan Institute for Clinical and Health Research (MICHR)UL1TR002240 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUMENG, JULIE C, MASHOUR, GEORGE ALEXANDER · 2017 to 2022
$54.9M
Impaired Endothelial Maturation and the Developmental Origin of Vascular DiseaseR01HD078639 · NICHD · JOHNS HOPKINS UNIVERSITY · PI FLAVAHAN, NICHOLAS A · 2014 to 2018
$1.7M
Outcomes Research in Rheumatic DiseasesK24AR063120 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KHANNA, DINESH · 2012 to 2022
$1.6M
Systemic Sclerosis-Associated Interstitial Lung Disease Response IndexR01AR070470 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KHANNA, DINESH · 2017 to 2019
$642k
NCATS NIH HHS UL1 TR002240NIAMS NIH HHS K24 AR063120NIAMS NIH HHS R01 AR070470NICHD NIH HHS R01 HD078639
6 · The paper itself

Abstract

objectiveIntravenous iloprost improves Raynaud's phenomenon (RP) and promotes healing of digital ulcers in systemic sclerosis (SSc; scleroderma). Despite a short half-life, its clinical efficacy lasts weeks. Endothelial adherens junctions, which are formed by VE-cadherin clustering between endothelial cells (ECs), regulate endothelial properties including barrier function, endothelial-to-mesenchymal transition (EndoMT), and angiogenesis. We undertook this study to investigate the hypothesis that junctional disruption contributes to vascular dysfunction in SSc, and that the protective effect of iloprost is mediated by strengthening of those junctions.

methodsDermal ECs from SSc patients and healthy controls were isolated. The effect of iloprost on ECs was examined using immunofluorescence, permeability assays, Matrigel tube formation, and quantitative polymerase chain reaction.

resultsAdherens junctions in SSc were disrupted compared to normal ECs, as indicated by reduced levels of VE-cadherin and increased permeability in SSc ECs (P < 0.05). Iloprost increased VE-cadherin clustering at junctions and restored junctional levels of VE-cadherin in SSc ECs (mean ± SD 37.3 ± 4.3 fluorescence units) compared to normal ECs (mean ± SD 29.7 ± 3.4 fluorescence units; P < 0.05), after 2 hours of iloprost incubation. In addition, iloprost reduced permeability of monolayers, increased tubulogenesis, and blocked EndoMT in both normal and SSc ECs (n ≥ 3; P < 0.05). The effects in normal ECs were inhibited by a function-blocking antibody that prevents junctional clustering of VE-cadherin.

conclusionOur data suggest that the long-lasting effects of iloprost reflect its ability to stabilize adherens junctions, resulting in increased tubulogenesis and barrier function and reduced EndoMT. These findings provide a mechanistic basis for the use of iloprost in treating SSc patients with RP and digital ulcers.

Indexed as

Adherens JunctionsAntigens, CDCadherin 5CadherinsCapillary PermeabilityCase-Control StudiesCells, CulturedEndothelial CellsEpithelial-Mesenchymal TransitionFemaleHumansIloprostMaleMiddle AgedNeovascularization, PhysiologicRaynaud DiseaseAntigens, CDCadherin 5CadherinsIloprostVasodilator Agents

Identifiers

PMID33001586
PMCPMC7914149
OpenAlexW3089795826

What OpenQuestion holds

Textmetadata
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.