Single nucleus transcriptomics reveals ITGA8-driven fibroblast remodeling in rheumatic valvular atrial fibrillation
Year: 2026
Type: article
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.
Source: iScience
Institutions: Shanghai Jiao Tong University, Shanghai Children's Medical Center, First Affiliated Hospital Zhejiang University, Zhejiang University, Shanghai Chest Hospital, Sichuan University, West China Hospital of Sichuan University, Wuxi People's Hospital, Nanjing Medical University, Ningxia Medical University, Ningxia Medical University General Hospital
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,240
OpenAlex ID: W7204873898