# Rosuvastatin attenuates airway inflammation and remodeling in a chronic allergic asthma model through modulation of the AMPKα signaling pathway

## TL;DR

Rosuvastatin reduces airway inflammation and remodeling in a mouse model of chronic allergic asthma by activating the AMPKα signaling pathway.

## Contribution

This study is the first to show that rosuvastatin reduces airway remodeling in chronic allergic asthma via AMPKα modulation.

## Key findings

- Rosuvastatin decreased goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy in asthmatic mice.
- Treatment reduced inflammatory cytokines, OVA-specific IgE, and angiogenesis-related factors in BALF and serum.
- Rosuvastatin increased phosphorylated AMPKα levels, inhibiting angiogenesis and airway remodeling.

## Abstract

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5’-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.