iScience. 2026 Sep 1;29(9):117310. doi: 10.1016/j.isci.2026.117310. eCollection 2026 Sep 18.
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.
PMID:42733494 | PMC:PMC13571147 | DOI:10.1016/j.isci.2026.117310