Overexpression Alleviates Oxidative Stress-induced Ferroptosis in Aortic Aneurysms Via Activation

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2024 May 13

PMID 38738239

Authors

Yunjun He

Xiaohui Wang

Donglin Li

Qianqian Zhu

Yilang Xiang

Yangyan He

Hongkun Zhang

Affiliations

Soon will be listed here.

Abstract

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 () and GATA-binding protein 1 () 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 (HO) 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 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 (, , and ) were upregulated in the thoracic aortic aneurysm (TAA) samples of the GSE9106 dataset. The HO treatment increased the MOVAS cells' iron content and oxidative stress, upregulated ALAS2 protein levels, and decreased the ferroptosis-related protein levels. overexpression reversed HO-induced apoptosis and increased the inflammatory cytokine levels. Additionally, the knockdown of partially reversed the protective mechanism of overexpressed on HO-induced ferroptosis.

Conclusions: overexpression reduced HO-induced oxidative damage and iron-induced apoptosis in MOVAS cells, and knockdown partially reversed this protective effect. These findings suggested that the and regulatory pathways may be potential therapeutic targets in aortic aneurysms.

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