Dataset Information

Spectral library-enhanced label-free proteome profiling highlights the critical role of the right atrium in persistent atrial fibrillation

ABSTRACT: Pulmonary veins (PVs) in the left atrium (LA) are a critical site for the initiation of atrial fibrillation (AF). However, the persistent AF (persAF) extends beyond the LA, encompassing both atrial chambers with widespread AF drivers that further promote AF. However, PV ablation remains a cornerstone of AF management. Considering high post-ablation AF recurrence rates in persAF patients, we hypothesized that the right atrium (RA) may play a significant role in the persistence of AF. In this study, we established a comprehensive reference spectral library for the analysis of the human cardiac proteome by data-independent acquisition mass spectrometry (DIA-MS) using material from donor hearts. Application of this library enabled time-efficient and robust analysis of the persAF proteome using RA appendages from patients. Our findings reveal the presence of canonical AF markers and processes within the RA in persAF. Additionally, we observed that the RA mirrors the LA at the proteomic level, losing RA-specific and gaining LA-specific signature proteins in persAF. We conclude that the RA plays a pivotal role in sustaining persAF, underscoring its importance in the clinical management of AF.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

DISEASE(S): Atrial Fibrillation

SUBMITTER: Christof Lenz

LAB HEAD: Christof Lenz

PROVIDER: PXD055180 | Pride | 2026-06-11

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	20240731_130636_2023_188_2023_70_S_Kestel_Reprocessing_Consolidated.sne	Other
	N_Voigt_5xHeart_ALL_281122.kit	Other
	N_Voigt_5xHeart_ALL_281122.tsv	Tabular
	S_Kestel_010323_060623_DIA_A_01_RA1_1_11463.d.zip	Other
	S_Kestel_010323_060623_DIA_A_02_RA2_1_11464.d.zip	Other

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Project description:Background: Horses and humans are among the few mammals prone to developing spontaneous atrial fibrillation (AF), both suffering from high recurrence rates after treatment. Treatment resistance is often attributed to functional, structural, and metabolic remodeling of the atria. The aim of this explorative study was to evaluate the molecular pathways associated with early stages of AF in horses and to compare the AF proteomes between horses and humans. Methods: We performed data-independent acquisition mass spectrometry on myocardial biopsies collected from the right atrium (RA), left atrium (LA), and left ventricular chamber (LV) in horses with early stages of naturally occurring persistent AF and controls (n=8 in each group). Results: We identified a total of 3400 quantifiable proteins, several of which were differentially regulated between AF horses and controls (268 in RA, 324 in LA, and 284 in LV, p<0.05). Pathway enrichment analyses identified changes in metabolic, contractile, and extracellular matrix (ECM) proteins. Atrial hypocontractility and ECM remodeling were confirmed by echocardiography and histology, respectively. Key proteomic changes in horses with AF overlapped with human AF public datasets, underscoring the translational relevance of the equine AF model. Particularly, contractile proteins, such as cardiac troponins (TNNT2), myosin (MYH6) and tropomyosin (TPM2), along with metabolic regulators as heat shock protein family A (HSPA4) and Proteasome 26S Subunit, Non-ATPase 13 (PSMD13) were shared between horses and humans with AF. Moreover, a significant increase in several ECM glycoproteins was detected in both species, highlighting the importance of early ECM remodeling that extends beyond the fibrotic changes often associated with AF. Conclusion: The horse and human cardiac proteome share similar AF-related changes. Metabolic, functional, and structural protein changes identified in early-stage AF may provide clues to pharmacological targets for preventing AF-associated atrial remodeling and improving treatment success across species.

Dataset Information

Spectral library-enhanced label-free proteome profiling highlights the critical role of the right atrium in persistent atrial fibrillation

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