PXD059963

PXD059963 is an original dataset announced via ProteomeXchange.

Title	Metformin Protects Against Persistent Atrial Fibrillation in an Equine Model
Description	Background: Horses are one of the few animals that spontaneously develop atrial fibrillation (AF), making them a powerful model for studying AF mechanisms and treatment effects. Despite the initial effectiveness of treatment in both horses and humans, AF-induced atrial remodelling compromises long-term success. Observational studies have suggested that metformin reduces the risk of AF, but its effects on progressive AF-induced atrial remodelling have not yet been evaluated in a high-fidelity large animal model. Methods: Here, we employed a longitudinal horse model of tachypacing-induced self-sustained AF to characterize the electrical, molecular, and metabolic atrial changes over four months of disease, with and without metformin treatment. Electrophysiological and multi-omic approaches were combined with histology, echocardiography, biochemical and mitochondrial analyses to evaluate disease progression and treatment response. Results: The horse model replicated critical aspects of AF-induced atrial remodelling observed in humans, including electrical and structural changes. Despite upregulation of metabolic genes and proteins in AF, no significant ultrastructural mitochondrial changes were detected. Metformin-treated horses were less susceptible to AF and sustained a less complex AF substrate in the right atrium after four months of disease. These effects were associated with increased activity of the metabolic regulator, AMP-activated kinase (AMPK) , changes in metabolic pathways and modulation of ion-channel gene expression. Metformin did not appear to alter left atrial substrate remodelling. Conclusion: Metformin treatment conferred electrical protection in both the early and later stages of AF in a translationally relevant preclinical model. These findings support metformin as a lead molecul ar for AF-prevention, warranting further mechanistic and clinical studies.
HostingRepository	PRIDE
AnnounceDate	2025-12-03
AnnouncementXML	Submission_2025-12-03_10:13:10.157.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joakim Bastrup
SpeciesList	scientific name: Equus caballus (Horse); NCBI TaxID: NEWT:9796;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-20 01:51:42	ID requested
⏵ 1	2025-12-03 10:13:10	announced

10.1161/CIRCEP.125.013850;

submitter keyword: electrophysiology, large animal model, atrial remodelling,AMPK, translational cardiology

Thomas Jepps
contact affiliation	Department of Biomedical Sciences, Jepps lab, University of Copenhagen, Denmark
contact email	tjepps@sund.ku.dk
lab head
Joakim Bastrup
contact affiliation	Department of Biomedical Sciences, University of Copenhagen, Denmark
contact email	joakimbastrup@hotmail.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059963
     1. Label: PRIDE project
     2. Name: Metformin Protects Against Persistent Atrial Fibrillation in an Equine Model