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

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 remodeling 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 remodeling 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. CONCLUSIONS: Our findings suggest that RA undergoes comparable AF-associated remodeling to LA, contributing to atrial proteome unification which represents a hallmark of persAF.