Basic/Translational Science -> Whole Animal Electrophysiology and Pharmacology (includes Neurohumoral Modulation) D-AB20 - New Mechanistic Insights on Arrhythmia Initiation and Perpetuation (ID 40) Abstract

D-AB20-03 - Elevated β1-adrenergic Receptor Autoantibody Levels Increase Atrial Fibrillation Susceptibility By Promoting Atrial Fibrosis On Human And Rabbits (ID 783)

 L. Zhang: Nothing relevant to disclose.


Background: Beta1-adrenergic receptor autoantibodies (β1ARAbs) have been identified as pathogenic factors of atrial fibrillation (AF), but the underlying pathogenesis is not well-known.
Objective: We assessed the hypothesis that elevated β1ARAb levels increase AF susceptibility by promoting atrial fibrosis.
Methods: A total of 70 patients with paroxysmal AF were continuously recruited. The serum levels of β1ARAbs and circulating fibrosis biomarkers were analyzed by Elisa. We further established a rabbit β1ARAb overexpression model. We conducted electrophysiological studies and multielectrode array recordings to evaluate the atrial effective refractory period (AERP), AF inducibility and electrical conduction. Echocardiography, HE staining and Masson's trichrome staining were performed to evaluate the atrial structural changes. WB and PCR were used to detect protein and mRNA expression alterations in TGF-β1, collagen I and collagen III.
Results: Patients with a larger left atrial diameter (LAD) had a higher β1ARAb level. The β1ARAb level was positively correlated with the LAD and the circulating biomarker levels. Compared with the control group, the rabbits in immune group showed the following: (1) enhanced heart rate, shortened AERP, increased AF inducibility and decreased conduction velocity; (2) enlarged LAD and elevated systolic dysfunction; (3) significant fibrosis in the left atrium; and (4) increased expression levels of TGF-β1, collagen I and collagen III.
Conclusion: Our clinical and experiential study showed that β1ARAbs participate in the development of AF and that the potential mechanism of AF development is related to the promotion of atrial fibrosis.