Evidence map›Paper›PMID 39098108›Full record

ArticleEBioMedicine2024

NR4A3 prevents diabetes induced atrial cardiomyopathy by maintaining mitochondrial energy metabolism and reducing oxidative stress.

Hong Peng, Jiali Yuan, Zhengshuai Wang, Binfeng Mo, Yihui Wang, Yuepeng Wang, Qunshan Wang

Abstract read
In one paragraph

Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

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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.

Hong PengDepartment of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Jiali YuanDepartment of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Zhengshuai WangDepartment of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Binfeng MoDepartment of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Yihui WangThe Department of Radiology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Yuepeng WangDepartment of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. Electronic address: wangyuepeng@xinhuamed.com.cn.
Qunshan WangDepartment of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. Electronic address: wangqunshan@xinhuamed.com.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAtrial cardiomyopathy (ACM) is responsible for atrial fibrillation (AF) and thromboembolic events. Diabetes mellitus (DM) is an important risk factor for ACM. However, the potential mechanism between ACM and DM remains elusive.

methodsAtrial tissue samples were obtained from patients diagnosed with AF or sinus rhythm (SR) to assess alterations in NR4A3 expression, and then two distinct animal models were generated by subjecting Nr4a3-/- mice and WT mice to a high-fat diet (HFD) and Streptozotocin (STZ), while db/db mice were administered AAV9-Nr4a3 or AAV9-ctrl. Subsequently, in vivo and in vitro experiments were conducted to assess the impact of NR4A3 on diabetes-induced atrial remodeling through electrophysiological, biological, and histological analyses. RNA sequencing (RNA-seq) and metabolomics analysis were employed to unravel the downstream mechanisms.

findingsThe expression of NR4A3 was significantly decreased in atrial tissues of both AF patients and diabetic mice compared to their respective control groups. NR4A3 deficiency exacerbated atrial hypertrophy and atrial fibrosis, and increased susceptibility to pacing-induced AF. Conversely, overexpression of NR4A3 alleviated atrial structural remodeling and reduced AF induction rate. Mechanistically, we confirmed that NR4A3 improves mitochondrial energy metabolism and reduces oxidative stress injury by preserving the transcriptional expression of Sdha, thereby exerting a protective influence on atrial remodeling induced by diabetes.

interpretationOur data confirm that NR4A3 plays a protective role in atrial remodeling caused by diabetes, so it may be a new target for treating ACM.

fundingThis study was supported by the major research program of National Natural Science Foundation of China (NSFC) No: 82370316 (to Q-S. W.), No. 81974041 (to Y-P. W.), and No. 82270447 (to Y-P. W.) and Fundation of Shanghai Hospital Development Center (No. SHDC2022CRD044 to Q-S. W.).

Indexed as

Diabetes Mellitus, ExperimentalEnergy MetabolismOxidative StressAnimalsAtrial FibrillationAtrial RemodelingCardiomyopathiesDiabetic CardiomyopathiesDisease Models, AnimalDNA-Binding ProteinsHeart AtriaHumansMaleMiceMice, KnockoutMitochondriaDNA-Binding ProteinsNR4A3 protein, humanReceptors, SteroidReceptors, Thyroid HormoneAtrial cardiomyopathyAtrial fibrillationEnergy metabolismMitochondriaNR4A3Oxidative stress

Identifiers

PMID39098108
PMCPMC11334830

What Socratic holds

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LicenceCC BY-NC-ND
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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.