Evidence map›Paper›PMID 39054558›Full record

ArticleArthritis research & therapy2024

Elevated neutrophil extracellular traps in systemic sclerosis-associated vasculopathy and suppression by a synthetic prostacyclin analog.

Neda Kortam, Wenying Liang, Claire Shiple, Suiyuan Huang, Rosemary Gedert, James St Clair, Cyrus Sarosh, Caroline Foster, Pei-Suen Tsou, John Varga and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. The Role of CXCL4 in Systemic Sclerosis: DAMP, Auto-Antigen and Biomarker.International journal of molecular sciences · 2025
    Review
  8. 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

13 authors.

Neda KortamDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Wenying LiangDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Claire ShipleDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Suiyuan HuangDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Rosemary GedertDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
James St ClairDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Cyrus SaroshDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Caroline FosterDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Pei-Suen TsouDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
John VargaDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Jason S KnightDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Dinesh KhannaDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA.
Ramadan A AliDivision of Rheumatology, Department of Internal Medicine, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI, 48109, USA. ramali@umich.edu.

Funding

Arthritis National Research Foundation AWD020851National Scleroderma Foundation AWD026059
6 · The paper itself

Abstract

objectivesNeutrophils and neutrophil extracellular traps (NETs) contribute to the vascular complications of multiple diseases, but their role in systemic sclerosis (SSc) is understudied. We sought to test the hypothesis that NETs are implicated in SSc vasculopathy and that treatment with prostacyclin analogs may ameliorate SSc vasculopathy not only through vasodilation but also by inhibiting NET release.

methodsBlood from 125 patients with SSc (87 diffuse cutaneous SSc and 38 limited cutaneous SSc) was collected at a single academic medical center. Vascular complications such as digital ulcers, pulmonary artery hypertension, and scleroderma renal crisis were recorded. The association between circulating NETs and vascular complications was determined using in vitro and ex vivo assays. The impact of the synthetic prostacyclin analog epoprostenol on NET release was determined.

resultsNeutrophil activation and NET release were elevated in patients with SSc-associated vascular complications compared to matched patients without vascular complications. Neutrophil activation and NETs positively correlated with soluble E-selectin and VCAM-1, circulating markers of vascular injury. Treatment of patients with digital ischemia with a synthetic prostacyclin analog boosted neutrophil cyclic AMP, which was associated with the blunting of NET release and reduced NETs in circulation.

conclusionOur study demonstrates an association between NETs and vascular complications in SSc. We also identified the potential for an additional therapeutic benefit of synthetic prostacyclin analogs, namely to reduce neutrophil hyperactivity and NET release in SSc patients.

Indexed as

EpoprostenolExtracellular TrapsScleroderma, SystemicAdultAgedFemaleHumansMaleMiddle AgedNeutrophil ActivationNeutrophilsVascular DiseasesEpoprostenolNeutrophil extracellular traps (NETs)ProstacyclinSystemic sclerosisVascular complications

Identifiers

PMID39054558
PMCPMC11270934

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.