Single nucleus transcriptomics reveals ITGA8-driven fibroblast remodeling in rheumatic valvular atrial fibrillation

Atrial fibrillation (AF) associated with rheumatic valvular disease involves complex cellular remodeling of the atrial myocardium. Here, single-nucleus RNA sequencing of left atrial tissues from healthy donors and patients with persistent rheumatic valvular AF identified disease-associated transcriptional changes across major cardiac cell populations. Fibroblasts showed marked heterogeneity, with expansion of an ITGA8-enriched FB-C2-ELN state associated with extracellular matrix remodeling. Functional experiments demonstrated that ITGA8 promotes cardiac fibroblast proliferation, migration, and matrix production. In an ACh/CaCl2-induced rat model, fibroblast-targeted ITGA8 suppression reduced atrial fibrosis and AF susceptibility. These findings define cellular states associated with atrial remodeling and highlight fibroblast ITGA8 signaling as a regulator of fibrosis-related AF progression.

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Publication Details

Journal
iScience
Published
2026-09-01
DOI
https://doi.org/10.1016/j.isci.2026.117310
Primary Topic
Congenital heart defects research
Type
article
Field-Weighted Citation Impact
0.00

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article

Single nucleus transcriptomics reveals ITGA8-driven fibroblast remodeling in rheumatic valvular atrial fibrillation

Zikun Wang, Weizhuo Liu, Yilin Pan, Yangyang Sun et al.
iScience
Congenital heart defects research
article

Single nucleus transcriptomics reveals ITGA8-driven fibroblast remodeling in rheumatic valvular atrial fibrillation

Zikun Wang, Weizhuo Liu, Yilin Pan, Yangyang Sun, Yangyang Zhang, Jingjing Liu, Jinjin Wu, Zhengjie Wang, Li Zhang, Yongjun Qian, Yuliang Wang, Lin Sun, Lei Yang
article en

Abstract

Atrial fibrillation (AF) associated with rheumatic valvular disease involves complex cellular remodeling of the atrial myocardium. Here, single-nucleus RNA sequencing of left atrial tissues from healthy donors and patients with persistent rheumatic valvular AF identified disease-associated transcriptional changes across major cardiac cell populations. Fibroblasts showed marked heterogeneity, with expansion of an ITGA8-enriched FB-C2-ELN state associated with extracellular matrix remodeling. Functional experiments demonstrated that ITGA8 promotes cardiac fibroblast proliferation, migration, and matrix production. In an ACh/CaCl2-induced rat model, fibroblast-targeted ITGA8 suppression reduced atrial fibrosis and AF susceptibility. These findings define cellular states associated with atrial remodeling and highlight fibroblast ITGA8 signaling as a regulator of fibrosis-related AF progression.

iScienceVol. 29(9)
Shanghai Jiao Tong University (CN), Sichuan University (CN), Shanghai Chest Hospital (CN), West China Hospital of Sichuan University (CN), Shanghai Children's Medical Center (CN), Ningxia Medical University (CN), Wuxi People's Hospital (CN), First Affiliated Hospital Zhejiang University (CN), Nanjing Medical University (CN)
National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality
Zero hunger
Openalex Percentile: Top 18%
Congenital heart defects research
DOIOpen Access PDFOpenAlex
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