Evidence map›Paper›PMID 39697901›Full record

ArticlePulmonary circulation2024

The hepcidin-ferroportin axis influences mitochondrial function, proliferation, and migration in pulmonary artery endothelial and smooth muscle cells.

Theo Issitt, Quezia K Toe, Sofia L Pedersen, Thomas Shackshaft, Maziah Mohd Ghazaly, Laura West, Nadine D Arnold, Abdul Mahomed, George W Kagugube, Latha Ramakrishnan and 3 more

Abstract read
In one paragraph

Article in Pulmonary circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

13 authors.

Theo IssittNHLI, Faculty of Medicine Imperial College London London UK.ORCID 0000-0002-9366-8362
Quezia K ToeNHLI, Faculty of Medicine Imperial College London London UK.ORCID 0000-0002-0209-873X
Sofia L PedersenNHLI, Faculty of Medicine Imperial College London London UK.
Thomas ShackshaftNHLI, Faculty of Medicine Imperial College London London UK.
Maziah Mohd GhazalyNHLI, Faculty of Medicine Imperial College London London UK.
Laura WestDepartment of Infection, Immunity & Cardiovascular Disease University of Sheffield Sheffield UK.
Nadine D ArnoldDepartment of Infection, Immunity & Cardiovascular Disease University of Sheffield Sheffield UK.
Abdul MahomedNHLI, Faculty of Medicine Imperial College London London UK.
George W KagugubeNHLI, Faculty of Medicine Imperial College London London UK.
Latha RamakrishnanNHLI, Faculty of Medicine Imperial College London London UK.
Allan LawrieNHLI, Faculty of Medicine Imperial College London London UK.ORCID 0000-0003-4192-9505
Gregory J QuinlanNHLI, Faculty of Medicine Imperial College London London UK.ORCID https://orcid.org/0000-0002-3305-3278
S John WortNHLI, Faculty of Medicine Imperial College London London UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Elevated circulating hepcidin levels have been reported in patients with pulmonary artery hypertension (PAH). Hepcidin has been shown to promote proliferation of human pulmonary artery smooth muscle cells (PASMCs) in vitro, suggesting a potential role in PAH pathogenesis. However, the role of human pulmonary artery endothelial cells (PAECs) as either a source of hepcidin, or the effect of hepcidin on PAEC function is not as well described. The objective of this study was to define the role of the hepcidin-ferroportin axis on the phenotype of PAEC and to study potential PAEC-PASMC interactions relevant to the pathogenesis of pulmonary vascular remodeling and PAH. PAECs treated with hepcidin, or interleukin-6 were investigated for both ferroportin and hepcidin release and regulation using immunofluorescence, mRNA levels and cellular release assays. Effects of hepcidin on PASMC and PAEC mitochondrial function was investigated using immunofluorescence and seahorse assay. Migration and proliferation of PASMCs treated with conditioned media from hPAEC treated with hepcidin was investigated using the xCELLigence system and other tools. We demonstrate in this study that PAECs express ferroportin; hepcidin treatment of PAECs resulted in mitochondrial iron accumulation and intracellular hepcidin biosynthesis and release. Conditioned media from hepcidin treated PAECs caused PASMCs to down-regulate ferroportin expression whilst promoting migration and proliferation. Inhibition of hepcidin in PAEC conditioned media limited these responses. PASMC cellular and mitochondrial iron retention are associated with migratory and proliferative responses. This study confirms that the hepcidin ferroportin axis is present and operational in PAECs. Modulation of this axis shows distinct differences in responses seen between PAECS and PASMCs. Stimulation of this axis in PAECs with hepcidin may well institute proliferative and migratory responses in PASMCs of relevance to pathogenesis of PAH offering potential novel therapeutic targets.

Indexed as

hepcidin ferroportin axisironmitochondriapulmonary artery hypertension

Identifiers

PMID39697901
PMCPMC11653027

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.