ArticleEBioMedicine2024
NR4A3 prevents diabetes induced atrial cardiomyopathy by maintaining mitochondrial energy metabolism and reducing oxidative stress.
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.
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Who cites it
18 citing papers in PubMed.
- Reconstructing AF-associated atrial fibrosis: Patient-specific iPSC models, fit-for-purpose atrial microphysiological systems, and nanomedicine.Materials today. Bio · 2026Review
- Innervated human cardiac muscle model reveals sympathetic drivers of KCNH2-associated arrhythmias.Nature communications · 2026Article
- Nr4a3 deficiency disrupts MEK1-ERK1/2-Drp1 signaling, driving adiposity and glucose intolerance in male mice.American journal of physiology. Endocrinology and metabolism · 2026Article
- HSPE1 promotes immune evasion in lung adenocarcinoma by mediating mitochondrial oxidative stress via histone lactylation-mediated SDHA transcriptional activation.Translational oncology · 2026Article
- The horse cardiac transcriptome: Moving towards a molecular understanding of atrial fibrillation.Equine veterinary journal · 2026Article
- Divergent mitochondrial and fibrotic signatures in atrial fibrillation: insights from organoids and GEO data.Cardiovascular diabetology · 2026Article
- Atrial Fibrillation in Diabetes: Epidemiology, Mechanisms and Integrated Management.Journal of clinical medicine · 2026Review
- NR4A3 alleviates diabetic neuropathy via GLS2-mediated mitochondrial repair and Schwann cell differentiation.iScience · 2026Article
- Impact of intracardiac echocardiography on radiofrequency catheter ablation for atrial fibrillation: a clinical study on procedural parameters and post-procedural recurrence.Frontiers in cardiovascular medicine · 2026Article
- Diabetic Atrial Cardiomyopathy: Pathogenesis, Diagnosis, Management, AI-Driven Diagnosis, and Risk Prediction.Journal of diabetes research · 2026Review
- Mitochondria transplantation mitigates attenuation of muscle fiber regeneration by evoked contractions.American journal of physiology. Cell physiology · 2026Article
- Gut-heart axis disruption and LPS translocation: driving atrial fibrillation through inflammatory storm and fibrotic mechanisms.Frontiers in endocrinology · 2026Review
- LAAEV-centric atrial failure phenotype and a novel integrative score for predicting early recurrence after AF ablation.Frontiers in cardiovascular medicine · 2026Article
- Prolonged Loss of Oxidative Phosphorylation and Mitochondrial Mass Characterize CD66bbioRxiv : the preprint server for biology · 2025Article
- Targeting ATF4-DDIT4/TXNIP induced mitochondrial dysfunction and ferroptosis: ISRIB as novel therapy for septic cardiomyopathy.Journal of translational medicine · 2025Article
- Neutrophil extracellular traps (NETs) are increased in rheumatoid arthritis-associated interstitial lung disease.Respiratory research · 2025Article
- Dilated Cardiomyopathy May Be Associated With a Novel Mitochondrial tRNAHuman mutation · 2025Article
- Higher premature atrial contraction burden after radiofrequency ablation vs. pulsed field or cryoballoon ablation in paroxysmal atrial fibrillation: a 3-year follow-up retrospective study.Frontiers in cardiovascular medicine · 2025Article
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7 authors.
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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.).
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