Alamandine Attenuates Hypoxia-Induced Atrial Fibrillation in Rats: Involvement of Endoplasmic Reticulum Stress and Pyroptosis Pathways

Chronic intermittent hypoxia (CIH) constitutes the primary pathophysiological disturbance in obstructive sleep apnoea (OSA), recognised as an independent risk factor for cardiovascular disease. The protective peptide alamandine (ALA), emerging as a novel component of the renin-angiotensin system, holds potential for elucidating molecular mechanisms underlying OSA-associated atrial fibrillation (AF). This study demonstrates that ALA treatment downregulates the expression of molecules associated with the GRP78/ATF6/CHOP pathway and pyroptosis-related proteins, while simultaneously mitigating atrial electrophysiological and structural remodelling and reducing susceptibility to AF. These findings suggest that the cardioprotective effects of ALA may be mediated through regulation of ERS and pyroptosis-related pathways, providing preliminary experimental evidence for its potential application in AF therapy. However, the precise molecular mechanisms require further functional validation.