Evidence map›Paper›PMID 35853948›Full record

ArticleScientific reports2022

Kynurenine metabolites predict survival in pulmonary arterial hypertension: A role for IL-6/IL-6Rα.

Zongye Cai, Siyu Tian, Theo Klein, Ly Tu, Laurie W Geenen, Thomas Koudstaal, Annemien E van den Bosch, Yolanda B de Rijke, Irwin K M Reiss, Eric Boersma and 8 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. 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
2.3field-weighted citation impact, top 11% 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, 17 citations in OpenAlex.

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  16. Article
  17. Kynurenine Pathway in Respiratory Diseases.International journal of tryptophan research : IJTR · 2024
    Review
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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

18 authors at 8 institutions in 5 countries.

Zongye CaiDepartment of Cardiology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Siyu TianDepartment of Cardiology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Theo KleinDepartment of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Ly TuINSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
Laurie W GeenenDepartment of Cardiology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Thomas KoudstaalDepartment of Pulmonary Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Annemien E van den BoschDepartment of Cardiology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Yolanda B de RijkeDepartment of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Irwin K M ReissDepartment of Pediatrics/Neonatology, Sophia Children's Hospital, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Eric BoersmaDepartment of Cardiology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Claude van der LeyLaboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Martijn Van FaassenLaboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ido KemaLaboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Dirk J DunckerDepartment of Cardiology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Karin A BoomarsDepartment of Pulmonary Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Karin Tran-LundmarkDepartment of Experimental Medical Science, Lund University, Lund, Sweden.
Christophe GuignabertINSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
Daphne MerkusDepartment of Cardiology, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. d.merkus@erasmusmc.nl.
Erasmus MC · NLUniversity Medical Center Groningen · NLInserm · FRLudwig-Maximilians-Universität München · DELund University · SESecond Affiliated Hospital of Zhejiang University · CNUniversité Paris-Saclay · FRUniversity of Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Activation of the kynurenine pathway (KP) has been reported in patients with pulmonary arterial hypertension (PAH) undergoing PAH therapy. We aimed to determine KP-metabolism in treatment-naïve PAH patients, investigate its prognostic values, evaluate the effect of PAH therapy on KP-metabolites and identify cytokines responsible for altered KP-metabolism. KP-metabolite levels were determined in plasma from PAH patients (median follow-up 42 months) and in rats with monocrotaline- and Sugen/hypoxia-induced PH. Blood sampling of PAH patients was performed at the time of diagnosis, six months and one year after PAH therapy. KP activation with lower tryptophan, higher kynurenine (Kyn), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), kynurenic acid (KA), and anthranilic acid was observed in treatment-naïve PAH patients compared with controls. A similar KP-metabolite profile was observed in monocrotaline, but not Sugen/hypoxia-induced PAH. Human lung primary cells (microvascular endothelial cells, pulmonary artery smooth muscle cells, and fibroblasts) were exposed to different cytokines in vitro. Following exposure to interleukin-6 (IL-6)/IL-6 receptor α (IL-6Rα) complex, all cell types exhibit a similar KP-metabolite profile as observed in PAH patients. PAH therapy partially normalized this profile in survivors after one year. Increased KP-metabolites correlated with higher pulmonary vascular resistance, shorter six-minute walking distance, and worse functional class. High levels of Kyn, 3-HK, QA, and KA measured at the latest time-point were associated with worse long-term survival. KP-metabolism was activated in treatment-naïve PAH patients, likely mediated through IL-6/IL-6Rα signaling. KP-metabolites predict response to PAH therapy and survival of PAH patients.

Indexed as

Interleukin-6KynureninePulmonary Arterial HypertensionReceptors, Interleukin-6AnimalsEndothelial CellsHumansHypoxiaKynurenic AcidMonocrotalineQuinolinic AcidRatsIL6 protein, humanIl6 protein, ratIL6R protein, humanInterleukin-6Kynurenic AcidKynurenineMonocrotalineQuinolinic AcidReceptors, Interleukin-6

Identifiers

PMID35853948
PMCPMC9296482
OpenAlexW4286217677

What OpenQuestion holds

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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.