Piezo2 expressed in ganglionated plexi: Potential therapeutic target of atrial fibrillation

Abstract

Background

Atrial fibrillation (AF) is closely linked to autonomic nervous system activity, with activation of the cardiac ganglionated plexi (GP) often present in AF. Piezo, a mechanosensitive ion channel, plays a pivotal role in neuronal modulation. However, its involvement in the GP and AF remains poorly understood.

Objective

This study investigated the expression of Piezo2 in GP and its potential role in AF.

Methods

GP tissues were collected from patients undergoing cardiac transplantation, and Piezo expression levels were assessed. Rapid atrial pacing was performed in a large-animal model to induce AF, and Piezo expression in GP tissues was also evaluated. Piezo2 knockdown in GP was achieved by adeno-associated virus in animals subjected to rapid atrial pacing. Atrial electrophysiologic parameters, AF inducibility, neural activity, and GP function were subsequently analyzed. RNA sequencing was employed to elucidate underlying mechanisms.

Results

In the AF group and in people with higher left atrial pressure, Piezo2 expression was increased in the GP. Knockdown of Piezo2 in GP impaired GP function and neural activity, thereby decreasing AF susceptibility. RNA sequencing analysis revealed significant downregulation of the Notch signaling pathway.

Conclusion

These findings suggest that Piezo2 expressed in GP may serve as a novel therapeutic target for the treatment of AF.