Background
Aortic aneurysm, characterized by abnormal dilation of the aorta, poses significant health risks. This study aims to investigate the interaction between 5-aminolevulinate synthase 2 (
ALAS2
) and GATA-binding protein 1 (
GATA1
) in ferroptosis and oxidative stress responses in aortic aneurysm.
Methods
A weighted gene co-expression network analysis (WGCNA) was performed on the differentially expressed genes (DEGs) within the GSE9106 dataset to identify the key module. Subsequently, protein-protein interaction (PPI) network analysis was performed on the key module. Mouse aortic vascular smooth muscle cells (MOVAS) were treated with hydrogen peroxide (H
2
O
2
) to induce oxidative stress, and ferroptosis inducers and inhibitors were added to evaluate their effects on iron content and oxidative stress markers. Through a series of
in
vitro
cellular experiments, we assessed cell viability, expression levels of GATA1 and iron mutation-associated proteins, as well as cellular phenotypes such as inflammatory responses and apoptosis rates.
Results
Three candidate genes (
ALAS2
,
GYPA
, and
GYPB
) were upregulated in the thoracic aortic aneurysm (TAA) samples of the GSE9106 dataset. The H
2
O
2
treatment increased the MOVAS cells’ iron content and oxidative stress, upregulated ALAS2 protein levels, and decreased the ferroptosis-related protein levels.
ALAS2
overexpression reversed H
2
O
2
-induced apoptosis and increased the inflammatory cytokine levels. Additionally, the knockdown of
GATA1
partially reversed the protective mechanism of overexpressed
ALAS2
on H
2
O
2
-induced ferroptosis.
Conclusions
ALAS2
overexpression reduced H
2
O
2
-induced oxidative damage and iron-induced apoptosis in MOVAS cells, and
GATA1
knockdown partially reversed this protective effect. These findings suggested that the
ALAS2
and
GATA1
regulatory pathways may be potential therapeutic targets in aortic aneurysms.