Key result
RNA-seq of AF LAA tissue reveals dedifferentiated cardiomyocytes, fewer endothelial progenitors, and amplified inflammation.
Why the study?
Tissue remodeling is a significant topic in atrial fibrillation, but its systematic transcriptional signature remains unclear.
What are the cellular-level molecular characteristics and transcriptional signatures in the left atrial appendage of patients with atrial fibrillation compared to sinus rhythm?
Observational
What are the cellular-level molecular characteristics and transcriptional signatures in the left atrial appendage of patients with atrial fibrillation compared to sinus rhythm?
Single-nuclei RNA sequencing of the left atrial appendage reveals distinct cellular remodeling in atrial fibrillation, including dedifferentiated cardiomyocytes and amplified inflammatory responses, providing potential novel therapeutic targets.
May guide targeted AF research on inflammation and remodeling; leaves open clinical translation from Level 5 data.
INTRODUCTION: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and it significantly increases the risk of cardiovascular complications and morbidity, even with appropriate treatment. Tissue remodeling has been a significant topic, while its systematic transcriptional signature remains unclear in AF. OBJECTIVES: Our study aims to systematically investigate the molecular characteristics of AF at the cellular-level. METHODS: We conducted single-nuclei RNA-sequencig (snRNA-seq) analysis using nuclei isolated from the left atrial appendage (LAA) of AF patients and sinus rhythm. Pathological staining was performed to validate the key findings of snRNA-seq. RESULTS: T cells with high pro-inflammatory score in LAA of AF. Furthermore, the analysis of intercellular communication revealed specific pathways related to AF, such as inflammation, extracellular matrix, and vascular remodeling signals. CONCLUSIONS: This study has discovered the presence of dedifferentiated CMs, a decrease in endothelial progenitor cells, a shift in the secretion profile of adipocytes, and an amplified inflammatory response in AF. These findings could offer crucial insights for future research on AF and serve as valuable references for investigating novel therapeutic approaches for AF.
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Sheng et al. (2023) conducted an observational in Atrial fibrillation. Atrial fibrillation (exposure) vs. Sinus rhythm was evaluated on Cellular-level molecular characteristics and transcriptional signatures. Single-nuclei RNA-sequencing of left atrial appendage tissue from atrial fibrillation patients revealed dedifferentiated cardiomyocytes, decreased endothelial progenitor cells, and amplified inflammation.
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