Evidence map›Paper›PMID 39609844›Full record

ArticleRespiratory research2024

Intestinal IFNα4 promotes 15-HETE diet-induced pulmonary hypertension.

Grégoire Ruffenach, Lejla Medzikovic, Laila Aryan, Wasila Sun, Long Lertpanit, Ellen O'Connor, Ateyeh Dehghanitafti, Mohammad Reza Hatamnejad, Min Li, Srinivasa T Reddy and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

11 authors.

Grégoire RuffenachDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, CHS BH-550 CHS, Los Angeles, CA, 90095-7115, USA. gr.ruffenach@laposte.net.
Lejla MedzikovicDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, CHS BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Laila AryanDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, CHS BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Wasila SunDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, CHS BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Long LertpanitDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-7115, USA.
Ellen O'ConnorDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-7115, USA.
Ateyeh DehghanitaftiDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, CHS BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Mohammad Reza HatamnejadDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, CHS BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Min LiDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, CHS BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Srinivasa T ReddyDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-7115, USA.
Mansoureh EghbaliDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, CHS BH-550 CHS, Los Angeles, CA, 90095-7115, USA. meghbali@ucla.edu.

Funding

Role of miR125 in pulmonary hypertension secondary to interstitial lung diseaseR01HL147586 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Mansoureh Eghbali · 2021 to 2023
$1.4M
Role of intestinal inflammation in oxidized lipid induced pulmonary hypertensionR01HL162124 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$611k
American Heart Association 20CDA35350059American Heart Association 20POST35210727American Heart Association 23POST1022457NHLBI NIH HHS R01 HL129051NHLBI NIH HHS R01 HL147586NHLBI NIH HHS R01 HL159865NHLBI NIH HHS R01 HL162124NIH HHS R01HL129051NIH HHS T32HL144449
6 · The paper itself

Abstract

objectivesPulmonary arterial hypertension (PAH) is characterized by the remodeling of the pulmonary vascular bed leading to elevation of the pulmonary arterial pressure. Oxidized fatty acids, such as hydroxyeicosatetraenoic acids (HETEs), play a critical role in PAH. We have previously established that dietary supplementation of 15-HETE is sufficient to cause PH in mice, suggesting a role for the gut-lung axis. However, the mechanisms are not known. APPROACH: Analysis of RNA-seq data obtained from the lungs and intestines of mice on 15-HETE diet together with transcriptomic data from PAH patient lungs identified IFN inducible protein 44 (IFI44) as the only gene significantly upregulated in mice and humans. We demonstrate that IFI44 is also significantly increased in PBMCs from PAH patients. In mice, 15-HETE diet enhances IFI44 and its inducer IFN⍺4 expression sequentially in the intestine first and then in the lungs. IFI44 expression in PAH is highly correlated with expression of Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL), which is upregulated in CD8 cells in PH lungs of both mice and humans. We show that IFNα4 produced by intestinal epithelial cells facilitates IFI44 expression in CD8 cells. Finally, we demonstrate that IFN receptor 1-KO in mice do not develop PH on 15-HETE diet. In addition, silencing IFI44 expression in the lungs of mice on 15-HETE diet prevents the development of PH and is associated with significantly lower expression of IFI44 and TRAIL in CD8 cells in the lungs.

conclusionOur data reveal a novel gut-lung axis driven by 15-HETE in PH.

Indexed as

Hydroxyeicosatetraenoic AcidsHypertension, PulmonaryMice, Inbred C57BLAnimalsDietFemaleHumansIntestinal MucosaMaleMice15-hydroxy-5,8,11,13-eicosatetraenoic acidHydroxyeicosatetraenoic Acids

Identifiers

PMID39609844
PMCPMC11606228

What Socratic holds

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LicenceCC BY
Read underepoch 390

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 Socratic graph.