Beta1-adrenergic receptor autoantibodies contributes to atrial remodeling by PTEN-mediated repression ofcardiomyocyte autophagy and aggravation of cardiomyocyte apoptosis

Abstract

Abstract Purpose β1 adrenergic receptor autoantibodies (β1-AAbs) can promote atrial electrical remodelling and structural remodelling, ultimately leading to the development of atrial fibrillation (AF). Phosphatase and tensin homologue (PTEN) has been confirmed to be involved in AF, but its role in β1-AAb-induced AF is unclear. This study aimed to investigate the involvement of PTEN in the occurrence and development of β1-AAb-induced AF and explore the potential mechanism underlying its effect. Methods A β1-AAb-induced AF rat model was established by active immunization. The first section was divided into 3 groups: the control group, β1-AAb group, and β1-AAb+bisoprolol group. The second section was divided into 3 groups: the control group, β1-AAb group, and β1-AAb+Oroxin B group. Serum levels of β1-AAb, atrial tissue levels of cyclic monophosphate (cAMP), atrial electrophysiological parameters, cardiac structure and function, mitochondrial structure, autophagy levels, cardiomyocyte apoptosis, and myocardial fibrosis were examined. Results The results showed that β1-AAb induced electro-anatomical remodelling of the atrium, inhibited autophagy and increased apoptosis in atrial tissue. Blocking β1-AR could partially offset these effects. β1-AAb decreased PTEN expression in the atrium. In addition, activating PTEN with a specific agonist (Oroxin B) could inhibit the AKT/mTOR and NF-κB signalling pathways, increase autophagy, reduce apoptosis, and significantly improve atrial remodelling. Conclusion β1-AAbs inhibit PTEN protein expression and activate downstream signalling mediators (AKT/mTOR and NF-κB), thereby inhibiting autophagy and increasing apoptosis, which are involved in atrial remodelling. Bisoprolol and PTEN agonists ameliorate these effects.