Evidence map›Paper›PMID 41795420›Full record

ArticleRedox biology2026

Neutrophil Irgm1 ameliorates sepsis-induced myocardial dysfunction by promoting Alox15 degradation.

Zeng Wang, Jiaxiang Sun, Mingyang Wang, Lai Wei, Fengyi Liu, Wenhua Liu, Yige Liu, Jiaxin Wang, Fujian Tan, Bo Yu and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 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

13 authors.

Zeng WangDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China.
Jiaxiang SunThe Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China; Department of Cardiothoracic Surgery, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 150023, China.
Mingyang WangDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China.
Lai WeiDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China.
Fengyi LiuThe Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China; Department of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Wenhua LiuCritical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Yige LiuDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China.
Jiaxin WangDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China.
Fujian TanDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China.
Bo YuDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; State Key Laboratory of Frigid Zone Cardiovascular Disease, Harbin Medical University, Harbin, Heilongjiang, 150081, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China. Electronic address: yubodr@163.com.
Zhiqiang LiDepartment of Cardiothoracic Surgery, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 150023, China. Electronic address: lizhiqiangganzh@yeah.net.
Shaohong FangDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; State Key Laboratory of Frigid Zone Cardiovascular Disease, Harbin Medical University, Harbin, Heilongjiang, 150081, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China. Electronic address: fangshaohong@hrbmu.edu.cn.
Yong SunDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Nangang District, Harbin, 150081, China. Electronic address: sunyong@hrbmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sepsis-induced myocardial dysfunction (SIMD), a severe sepsis complication, is characterized by immune dysregulation, with neutrophils playing a central role. While the immunity-related GTPase family M protein (IRGM) in humans and its murine ortholog Irgm1 are key immune regulators, the precise contribution of neutrophil Irgm1 to SIMD pathogenesis remains unclear. This study aims to explore the involvement of neutrophil Irgm1 in SIMD and uncover its mechanisms. This research found that IRGM expression was upregulated in peripheral blood neutrophils from patients with SIMD and inversely correlated with disease severity. In mice, neutrophil-specific Irgm1 deficiency worsened CLP-induced cardiac dysfunction and myocardial inflammation. Mechanistically, Irgm1 interacted with the E3 ubiquitin ligase RING finger protein 213 (RNF213) to facilitate 15-lipoxygenase (Alox15) ubiquitination and degradation, thereby inhibiting neutrophil ferroptosis and suppressing the production of 15-HETE, which alleviates SIMD. In patients with SIMD, the expression levels of Alox15 and the concentrations of 15-HETE were positively correlated with disease severity. Notably, intraperitoneal administration of Alox15-targeting drug PD146176 significantly improved cardiac function in SIMD mice. Collectively, this study highlights the pivotal role of the Irgm1 in attenuating SIMD by restraining neutrophil ferroptosis and 15-HETE production. Irgm1 may serve as a promising prognostic biomarker and a valuable therapeutic target for SIMD.

Indexed as

Arachidonate 15-LipoxygenaseCardiomyopathiesGTP-Binding ProteinsNeutrophilsSepsisAnimalsArachidonate 12-LipoxygenaseDisease Models, AnimalHumansMaleMiceMyocardiumProteolysisUbiquitinationUbiquitin-Protein LigasesALOX15 protein, humanAlox15 protein, mouseArachidonate 12-LipoxygenaseArachidonate 15-LipoxygenaseGTP-Binding ProteinsIfi1 protein, mouseUbiquitin-Protein LigasesAlox15FerroptosisIRGM/Irgm1NeutrophilSepsis-induced myocardial dysfunctionUbiquitination

Identifiers

PMID41795420
PMCPMC12993022

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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.