Evidence mapPaperPMID 41812233Full record

ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2026

Fto-mediated m6A demethylation of Lox drives atrial fibrosis and promotes atrial fibrillation in a murine model of hyperthyroidism.

Han Gong, Chun Zhou, Ruopeng Tan, Lin Wang, Qi Su, Yang Liu, Xiaomeng Yin

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Article in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 citing paper in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Han GongInstitute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Rd, Dalian, China.ORCID 0000-0003-3372-2221
Chun ZhouInstitute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Rd, Dalian, China.
Ruopeng TanInstitute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Rd, Dalian, China.ORCID 0000-0002-8972-1466
Lin WangInstitute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Rd, Dalian, China.ORCID 0009-0004-1821-2316
Qi SuInstitute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Rd, Dalian, China.
Yang LiuInstitute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Rd, Dalian, China.
Xiaomeng YinDepartment of Cardiology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Rd, Dalian, China.ORCID 0000-0003-3565-893X

Funding

National Natural Science Foundation of China 82470322
6 · The paper itself

Abstract

aimsHyperthyroidism is a risk factor for atrial fibrillation (AF), and N6-methyladenosine (m6A) RNA methylation is crucial in cardiovascular regulation. However, the role of Fto-mediated m6A demethylation in hyperthyroidism-related AF remains unclear. METHODS AND

resultsWe consecutively recruited 232 AF patients undergoing ablation, stratified into age-, gender-, and comorbidity-matched cohorts, 116 with manifest hyperthyroidism and 116 without manifest hyperthyroidism. Assessments included thyroid profiles, echocardiography, low-voltage area (LVA) mapping, and 1-year recurrence. T4-treated mice with cardiomyocyte-specific Fto knockout or AAV9-mediated Fto overexpression were used. Electrophysiological and structural properties were assessed via electrical mapping and echocardiography. Mechanisms were further investigated in neonatal rat atrial myocytes (NRAMs). The hyperthyroid group showed higher 1-year recurrence (19.8 vs. 5.2%, P < 0.001) and larger LVA (27.81 vs. 20.25%, P < 0.001). Hyperthyroidism independently predicted LVA expansion (odds ratio = 2.868, P < 0.001). In mice, Fto up-regulation increased atrial fibrosis and AF susceptibility, while its deletion attenuated T4-induced atrial fibrosis and AF. Wild-type Fto overexpression promoted AF via m6A-dependent enhancement of lysyl oxidase (Lox) expression. Studies in NRAMs demonstrated that Fto enhanced the transcription and translation of Lox by reducing m6A methylation on Lox mRNA. Lox inhibition with BAPN suppressed fibrosis and AF inducibility.

conclusionHyperthyroidism promoted atrial arrhythmogenicity through Fto-mediated m6A demethylation of Lox, increasing Lox expression and atrial fibrosis. Targeting Fto-m6A-Lox may offer a novel therapy for hyperthyroidism-associated AF.

Indexed as

Alpha-Ketoglutarate-Dependent Dioxygenase FTOAtrial FibrillationHeart AtriaHyperthyroidismAnimalsDemethylationDisease Models, AnimalFemaleFibrosisHumansMaleMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacRNA MethylationAlpha-Ketoglutarate-Dependent Dioxygenase FTOFTO protein, mouseAtrial fibrillationDemethylaseHyperthyroidismm6A methylation modification

Identifiers

PMID41812233
PMCPMC13127892

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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 Socratic graph.