# IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts

## TL;DR

This study explores how IL-11 worsens atrial fibroblast dysfunction caused by Ang-II, potentially offering new targets for treating atrial fibrillation.

## Contribution

The novel finding is that IL-11 exacerbates Ang-II-induced autophagy inhibition and mitochondrial dysfunction through the mTOR pathway in atrial fibroblasts.

## Key findings

- IL-11 overexpression amplifies Ang-II-induced oxidative stress and mitochondrial dysfunction in atrial fibroblasts.
- IL-11 enhances Ang-II-induced autophagy inhibition via upregulation of the mTOR pathway.
- IL-11 promotes myofibroblast differentiation by increasing alpha-smooth muscle actin and p62 expression.

## Abstract

This study aimed to investigate potential targets for the pathogenesis of atrial fibrillation to facilitate the development of effective treatments. Atrial fibroblasts were isolated and stimulated with 1 μM angiotensin-II (Ang-II) for 24 h. To increase interleukin 11 (IL-11) expression, overexpression plasmids were transfected into atrial fibroblasts. The role and the underlying mechanism of IL-11 in atrial fibrillation were examined by immunofluorescence, measurements of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), and western blotting assays. Results demonstrated that IL-11 was upregulated in Ang-II-elicited atrial fibroblasts. Ang-II treatment increases alpha-smooth muscle actin (α-SMA), ROS and MMP levels, and p62 expression but decreases microtubule-associated protein light chain 3 II/I (LC3 II/I) and Beclin-1 expressions in atrial fibroblasts. These effects were further amplified by IL-11 overexpression. Mechanistically, the mammalian target of rapamycin (mTOR) pathway expression was enhanced in Ang-II-induced atrial fibroblasts, which was further elevated by IL-11 upregulation. IL-11 facilitates Ang II-induced differentiation of atrial fibroblasts into myofibroblasts by promoting oxidative stress, mitochondrial dysfunction, and autophagy inhibition through the mTOR pathway.