Evidence map›Paper›PMID 42206956›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Brown Adipocyte Sheets Alleviate Myocardial Ischemia-Reperfusion Injury Through NRG4-ErbB4-Dependent Ferroptosis Inhibition.

Lifu Sun, Yuting Liu, Jingbo Zhang, Takuji Kawamura, Junjun Li, Li Liu, Shigeru Miyagawa

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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. 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

7 authors.

Lifu SunDepartment of Cardiovascular Surgery, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.ORCID https://orcid.org/0000-0001-5254-2483
Yuting LiuDepartment of Cardiovascular Surgery, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.
Jingbo ZhangDepartment of Cardiovascular Surgery, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.
Takuji KawamuraDepartment of Cardiovascular Surgery, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.
Junjun LiPhotonics Cell Evaluation Laboratory, Graduate School of Engineering, The University of Osaka, Suita, Osaka, Japan.ORCID https://orcid.org/0000-0002-7473-4918
Li LiuPhotonics Cell Evaluation Laboratory, Graduate School of Engineering, The University of Osaka, Suita, Osaka, Japan.
Shigeru MiyagawaDepartment of Cardiovascular Surgery, Graduate School of Medicine, The University of Osaka, Suita, Osaka, Japan.

Funding

Grants-in-Aid for Scientific Research 25K12091Grants-in-Aid for Scientific Research 25K15894Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research 25K02725
6 · The paper itself

Abstract

Myocardial ischemia-reperfusion (I/R) injury causes cardiomyocyte death and cardiac dysfunction in part through ferroptosis. Brown adipocytes (BAs) have emerged as endocrine regulators with cardioprotective potential, yet their involvement in ferroptosis modulation during I/R injury remains unclear. Here, we engineered BA sheets and transplanted them onto the ischemic myocardium in a rat I/R model to evaluate therapeutic efficacy. BA sheets transplantation significantly improved cardiac function, reduced infarct size and fibrosis, and mitigated adverse remodeling while enhancing angiogenesis. In vitro, conditioned medium derived from BA sheets promoted cardiomyocyte survival, preserved contractile performance, and inhibited apoptosis and ferroptosis under hypoxia/reoxygenation stress. Mechanistically, these effects were mediated by the activation of the NRG4-ErbB4 axis and its downstream PI3K/AKT and NRF2/HO-1 antioxidant signaling pathways. Our findings demonstrate that engineered BA sheets exert potent cardioprotection against myocardial I/R injury by suppressing ferroptosis in an NRG4-ErbB4-dependent manner, supporting their promise as a therapeutic strategy for ischemic heart disease.

Indexed as

Adipocytes, BrownFerroptosisMyocardial Reperfusion InjuryNeuregulinsReceptor, ErbB-4AnimalsDisease Models, AnimalMaleMyocytes, CardiacRatsRats, Sprague-DawleySignal TransductionErbb4 protein, ratneuregulin-4NeuregulinsReceptor, ErbB-4brown adipocyte sheetsferroptosismyocardial ischemia–reperfusion injuryNRG4–ErbB4

Identifiers

PMID42206956
PMCPMC13336044

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.