Stone Elijah, Taylor Jude, Li Amy, McLachlan Craig S
Centre for Healthy Futures, Torrens University Australia, Surry Hills, New South Wales 2010, Australia.
Department of Rural Clinical Sciences, La Trobe University - Bendigo Campus, Bendigo, Victoria 3552, Australia.
R Soc Open Sci. 2025 Mar 5;12(3):241102. doi: 10.1098/rsos.241102. eCollection 2025 Mar.
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.
心房颤动（AF）可表现为持续性或永久性，每种形式都具有独特的病理特征。本研究探讨了与持续性和永久性AF相比，窦性心律对照组中心脏和免疫细胞相关的基因特征。我们进行了一项荟萃分析，以合并持续性和永久性AF左心房组织的独立微阵列和RNA测序（RNAseq）数据集。使用Cibersort和CibersortX推断细胞类型丰度，并使用ShinyGo进行基因集富集分析。在持续性AF中，观察到心房心肌细胞和平滑肌细胞显著减少，同时成纤维细胞、髓样细胞和周细胞增加。永久性AF显示内皮细胞和周细胞丰度增加。免疫细胞分析显示持续性AF中有五种细胞类型的丰度发生改变，特别是中性粒细胞增加，而永久性AF中未观察到这种情况。通路分析确定持续性AF中中性粒细胞激活和脱颗粒富集，而永久性AF中细胞外基质组织和血管生成通路富集。总之，本研究强调了慢性AF之间不同且复杂的免疫和细胞动态，其中持续性AF具有增强的免疫细胞浸润和中性粒细胞活性，这有助于维持AF，而永久性AF显示炎症恢复到基线，但组织重塑和血管生成增强。
