Evidence map›Paper›PMID 41429340›Full record

ArticleJournal of advanced research2026

Multi-omics analysis of early reperfused ischemic heart reveals ERRβ/γ activation protects against acute myocardial infarction injury.

Yun Gao, Fei Huang, Yuan Zhang, Dongwu Lai, Jiuxiao Zhao, Yuwen Lu, Liyin Shen, Fanwei Ruan, Zhe Zhang, Jin He and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

16 authors.

Yun GaoInstitute of Genetics and Reproduction, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Fei HuangThe MOE Key Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory of Molecular Cancer Biology, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Yuan ZhangInstitute of Genetics and Reproduction, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Dongwu LaiZhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Jiuxiao ZhaoInstitute of Genetics and Reproduction, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Yuwen LuThe MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China.
Liyin ShenThe MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China.
Fanwei RuanThe MOE Key Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory of Molecular Cancer Biology, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Zhe ZhangInstitute of Genetics and Reproduction, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Jin HeInstitute of Genetics and Reproduction, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Yan LiuInstitute of Genetics and Reproduction, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Ling TaoDepartment of Cardiology, Xijing Hospital, the Fourth Military Medical University, 127 Changle West Road, Xi'an 710032 Shaan Xi, China.
Guosheng FuZhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China. Electronic address: fugs@zju.edu.cn.
Yang ZhuZhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China; The MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310009, China. Electronic address: zhuyang@zju.edu.cn.
Li ShenThe MOE Key Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory of Molecular Cancer Biology, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310009, China; Department of Orthopedics Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China. Electronic address: li_shen@zju.edu.cn.
Lenan ZhuangInstitute of Genetics and Reproduction, Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China; ZJU-Xinchang Joint Innovation Centre (TianMu Laboratory), Gaochuang Hi-Tech Park, Xinchang 312500, China. Electronic address: zhuangln@zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAcute myocardial infarction (AMI) is a leading cause of morbidity and mortality globally, with timely percutaneous coronary intervention (PCI) as the standard treatment. Early time reperfusion (ETR) shown to reduce arrhythmias and improved survival rates compared to late time reperfusion (LTR). However, cellular and molecular mechanisms underlying the protective effects of ETR effects relative to LTR on AMI remain poorly understood.

objectivesThis study aims to elucidate these mechanisms through an integrated multi-omics approach, focusing on cardiomyocyte energenesis and dedifferentiation, while also exploring the therapeutic potential of ERRβ/γ activation.

methodsAMI was induced in rats by ligating the left anterior descending coronary artery (LAD) for one hour (ETR) or six hours (LTR), followed by reperfusion. Sham-operated rats served as controls. Comprehensive analyses of the ischemic hearts were performed using bulk tissue transcriptomic sequencing, metabolomic profiling, and single-nucleus RNA sequencing. Additionally, the role of ERRβ and ERRγ was investigated in neonatal rat ventricular myocytes (NRVMs) subjected to hypoxia/reoxygenation (H/R). The ERRβ/γ agonist GSK4716 was administered in vivo before ETR to assess its potential to enhance the therapeutic effects of ETR on AMI injury, and its protective mechanism was compared to fenofibrate.

resultsTranscriptomic and metabolomic profiling revealed that the protective effect of ETR on AMI relative to LTR is primarily mediated by cardiomyocyte energenesis and dedifferentiation. Single-nucleus RNA sequencing identified four distinct cardiomyocyte subpopulations (CM1-CM4), with ETR preserving a larger proportion of sub-injured CM2 and immature-like CM4. Additionally, ERRβ/γ was found to regulate the expression of cardiomyocyte energenesis and dedifferentiation signature genes both in vivo and in vitro. Treatment with the ERRβ/γ agonist GSK4716 significantly enhanced ETR's protective effects on AMI relative to LTR by activating energenesis and dedifferentiation-associated genes.

conclusionThese findings indicate that ETR protects against AMI relative to LTR by preserving cardiomyocyte energenesis and dedifferentiation. The activation of ERRβ/γ significantly enhanced these protective effects, highlighting its therapeutic potential in mitigating AMI outcomes.

Indexed as

Myocardial InfarctionMyocardial Reperfusion InjuryReceptors, EstrogenAnimalsDisease Models, AnimalMaleMetabolomicsMultiomicsMyocytes, CardiacRatsRats, Sprague-DawleyReceptors, EstrogenAcute myocardial infarction injuryDedifferentiationEnergenesisERRβ/γGSK4716Multi-omics sequencing

Identifiers

PMID41429340
PMCPMC13539260

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.