Mass spectrometric proteome profiling using a deep spectral library reveals homogenization of right and left atrial proteomes in persistent atrial fibrillation patients

Year: 2026

Type: article

Abstract: AIMS: Pulmonary veins in the left atrium (LA) are well-established as a critical site for the initiation of atrial fibrillation (AF). Emerging evidence suggests that in persistent AF (persAF), AF triggers may extend beyond LA. However, the extent to which AF-associated remodelling involves the right atrium (RA) in persAF remains a subject of debate. To address this, we employed a proteomic approach aiming at investigating AF-associated remodelling in the RA relative to the LA in persAF. METHODS AND RESULTS: RA and LA samples were obtained from sinus rhythm (SR) patients, patients with persAF undergoing open-heart surgery, and non-failing donor hearts rejected for transplantation. A reference spectral library representing the human cardiac proteome was employed to assess the RA and LA proteomes by data-independent acquisition mass spectrometry. Protein levels were quantified by immunoblotting of human atrial tissue. Plasma levels of NT-proANP and NT-proBNP were measured in SR and persAF patients. Fibrosis levels were quantified in paraffin-embedded sections using Masson-Goldner trichrome staining. A spectral library representing 13 539 human proteins was generated from five anatomical regions of five independent donor hearts. In persAF RA, we observed marked myolysis, excessive extracellular matrix deposition and a prominent similarity to the failing ventricular proteome, all comparable to persAF LA. Although significant proteomic differences were observed between the RA and LA from SR patients, a comparison of RA and LA proteomes in persAF patients revealed proteome homogenization between the two atrial chambers. RA contributes to this homogenization by losing RA-specific markers, while gaining LA-specific markers. CONCLUSION: Our findings suggest that RA undergoes comparable AF-associated remodelling to LA, contributing to atrial proteome unification which represents a hallmark of persAF.

Source: Cardiovascular Research

DOI: 10.1093/cvr/cvag076

Institutions: Universitätsmedizin Göttingen, German Centre for Cardiovascular Research, Multiscale Bioimaging, University of Göttingen, Inserm, Université Paris Cité, Paris Cardiovascular Research Center, Max Planck Institute for Multidisciplinary Sciences, Northwestern University, Heidelberg University, University Hospital Heidelberg, George Washington University, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, Vrije Universiteit Amsterdam

Language: English

Topic: Atrial Fibrillation Management and Outcomes

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,329

Funders: Deutsches Zentrum für Herz-Kreislaufforschung, Deutsche Forschungsgemeinschaft, Fondation Leducq, Fondation pour la Recherche Médicale, Hartstichting, Nederlandse Organisatie voor Wetenschappelijk Onderzoek

OpenAlex ID: W7148872625