Evidence map›Paper›PMID 41765931›Full record

ArticleBiology of sex differences2026

Hepatocyte growth factor may contribute to male protection against pulmonary arterial hypertension.

Lejla Medzikovic, Grégoire Ruffenach, Ateyeh Dehghanitafti, Brenda Wong, Ashley Ryder, Mohammad Reza Hatamnejad, Wasila Sun, Leana Esdin, Joshua Eghbali, Adam Brownstein and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of sex differences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

14 authors.

Lejla MedzikovicDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA. lmedzikovic@ucla.edu.
Grégoire Ruffenach *Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Ateyeh Dehghanitafti *Division of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Brenda WongDivision of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Ashley RyderDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, 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 Los Angeles, 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 Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Leana EsdinDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Joshua EghbaliDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Adam BrownsteinDivision of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Asif RazeeDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Soban UmarDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA.
Jason HongDivision of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Mansoureh EghbaliDivision of Molecular Medicine, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California Los Angeles, BH-550 CHS, Los Angeles, CA, 90095-7115, USA.

Funding

Investigating the molecular mechanisms of right ventricular failure in pulmonary hypertensionR01HL161038 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Soban Umar · 2022 to 2026
$1.9M
Role of Chromosome Y gene, Uty, in protecting against Pulmonary HypertensionR01HL159865 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI EGHBALI, MANSOUREH · 2021 to 2024
$1.9M
ZFP36, an RNA Binding Protein that Regulates DNA Repair and Cell Proliferation in PAHR01HL174472 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Mansoureh Eghbali · 2024 to 2026
$1.2M
Integrative Multiomics to Uncover Novel Genes and Networks in Pulmonary Arterial HypertensionK08HL169982 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jason Hong · 2023 to 2026
$706k
American Heart Association 24CDA1263497national insitutes of health K08HL169982NHLBI NIH HHS K08 HL169982NHLBI NIH HHS R01 HL161038NHLBI NIH HHS R01 HL174472NIH HHS R01HL159865
6 · The paper itself

Abstract

backgroundPulmonary arterial hypertension (PAH) presents as increased pressure in the pulmonary arteries (PA) leading to cardiac right ventricular (RV) failure and death. Pulmonary arterial (PA) remodeling characterized by enhanced proliferation of pulmonary arterial smooth muscle cells (PASMC) and fibroblasts (PAFB) underlies PAH. There are currently no cures and PAH mortality remains high. PAH has a striking female-predominant incidence - 4:1 ratio - indicating that males may have a protective factor. However, to date only a few sex-biased factors in PAH have been investigated.

methodsAnalyses were performed on a publicly available microarray dataset (GSE117261), comprising human lung tissues from PAH patients and healthy controls, as well as publicly available single-cell lung atlases of humans and mice. Lung tissue, plasma, PASMC and PAFB were collected from male and female PAH patients. Cell proliferation was assessed after recombinant HGF protein stimulation. PH was induced in male and female rats by monocrotaline (MCT). Lung-specific knockdown was performed by intratracheal siRNA instillation the first two weeks after MCT injection. PA and RV function were assessed by echocardiography, RV systolic pressure by catheterization, and PA remodeling by histology.

resultsHGF was only upregulated in lungs of male PAH patients compared to male control lungs, but not in female PAH patients vs. female controls. Elevated plasma HGF correlated with favorable clinical characteristics only in male PAH patients. HGF is highly expressed in vascular SMC and FB in the lung and recombinant HGF inhibited PASMC and PAFB proliferation to a greater extent in cells isolated from male PAH patients compared to female. Lung HGF expression is increased to a higher extent and longer duration at early stage of PH in male rats in MCT model vs. female rats. Finally, knockdown of HGF in the lungs in early disease stage exacerbated PH in male rats characterized by higher mortality, worsened RV and PA function as well as enhanced PA medial thickening and adventitial fibrosis.

conclusionsLung HGF expression may be upregulated to counteract PAH disease progression by inhibiting proliferation of PASMC and PAFB. Elevated HGF in males might at least partially account for the lower incidence of male PAH patients.

Indexed as

Hepatocyte Growth FactorHypertension, PulmonarySex CharacteristicsAnimalsCell ProliferationFemaleHumansLungMaleMiceMonocrotalinePulmonary ArteryRatsRats, Sprague-DawleyHepatocyte Growth FactorMonocrotaline

Identifiers

PMID41765931
PMCPMC13059264

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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.