# Transcriptional meta-analysis and immune cell profiles reveal altered neutrophil dynamics in chronic atrial fibrillation

## TL;DR

This study finds that persistent atrial fibrillation has increased neutrophil activity and immune cell infiltration, while permanent atrial fibrillation shows tissue remodeling and angiogenesis.

## Contribution

The study reveals distinct immune and cellular dynamics between persistent and permanent atrial fibrillation using transcriptional meta-analysis and immune cell profiling.

## Key findings

- Persistent AF shows increased neutrophils and immune cell infiltration with reduced cardiomyocytes and smooth muscle cells.
- Permanent AF is characterized by increased endothelial cells and pericytes with enriched extracellular matrix and angiogenesis pathways.
- Neutrophil activation and degranulation are specifically enriched in persistent AF but not in permanent AF.

## Abstract

Atrial fibrillation (AF) can present as persistent or permanent forms with each
exhibiting distinct pathological features. This study explores the gene
signatures associated with cardiac and immune cells in persistent and permanent
AF compared to sinus rhythm controls. We performed a meta-analysis to combine
independent microarray and RNA sequencing (RNAseq) datasets for both persistent
and permanent AF left atrial tissue. Cell type abundances were inferred using
Cibersort and CibersortX, and gene set enrichment analysis was performed using
ShinyGo. In persistent AF, a significant reduction in atrial cardiomyocytes and
smooth muscle cells, along with an increase in fibroblasts, myeloid cells and
pericytes was observed. Permanent AF showed increased endothelial cell and
pericyte abundance. Immune cell analysis revealed altered abundances in five
cell types in persistent AF, particularly an increase in neutrophils, which was
not observed in permanent AF. Pathway analysis identified enriched neutrophil
activation and degranulation in persistent AF, while permanent AF was enriched
in extracellular matrix organization and angiogenesis pathways. In conclusion,
this study highlights distinct and complex immune and cellular dynamics between
chronic AF, where persistent AF has heightened immune cell infiltration and
neutrophil activity which contribute to sustaining AF, whereas permanent AF
shows inflammation returning to baseline but enhanced tissue remodelling and
angiogenesis.