Key result
Orai3 deficiency exacerbates Ang II-induced atrial dilation, fibrosis, and structural damage in AF models.
Why the study?
The role of the Orai3 calcium channel in atrial remodeling and atrial fibrillation susceptibility was unexplored despite its regulation of cardiac homeostasis.
Orai3 modulation in rat AF models warrants no clinical action; leaves open its therapeutic relevance in human atrial remodeling.
AIMS: Atrial remodeling is the pathological substrate for atrial fibrillation (AF), yet no targeted therapies exist. The Orai3 calcium channel regulates cardiac homeostasis, but its role in atrial remodeling remains unexplored. METHODS: Wild type and Orai3 knockout rats were subjected to Angiotensin II infusion or acetylcholine‑calcium chloride injection to model atrial fibrosis and AF. Cardiac function, Orai channel related protein expression and co-localization, SOCE activity, and downstream signaling were evaluated by echocardiography, histology, immunofluorescence, calcium imaging, and western blotting. RESULTS: Orai3 deficiency exacerbated Ang II induced atrial dilation, fibrosis, and ultrastructural damage, with transcriptomic analysis revealing enrichment of extracellular matrix pathways. Mechanistically, Orai3 loss was associated with reduced Orai1/Orai3 co-localization and enhanced Orai1/STIM1 co-localization, driving SOCE hyperactivation. This aberrant Ca CONCLUSIONS: Orai3 acts as an endogenous protective brake against atrial cardiomyopathy. The Orai3-SOCE-TGF-β/Cx43 axis links calcium dyshomeostasis to both fibrotic and electrical remodeling, positioning Orai3 as a potential prognostic biomarker and therapeutic target for AF.
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Wu et al. (2026) studied Atrial fibrillation and remodeling. Orai3 knockout vs. Wild type was evaluated on Atrial dilation, fibrosis, and ultrastructural damage. Orai3 deficiency exacerbated Angiotensin II-induced atrial dilation, fibrosis, and ultrastructural damage in rat models of atrial fibrillation.
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