Exploring the molecular biology of ischemic cardiomyopathy based on ferroptosis‑related genes

Shi-Tao Zhao; Zhi-Cong Qiu; Rui-Yuan Zeng; Hua-Xi Zou; Rong-Bin Qiu; Han-Zhi Peng; Lian-Fen Zhou; Zhi-Qiang Xu; Song-Qing Lai; Li Wan

doi:10.3892/etm.2024.12509

Exploring the molecular biology of ischemic cardiomyopathy based on ferroptosis‑related genes

Exp Ther Med. 2024 Mar 22;27(5):221. doi: 10.3892/etm.2024.12509. eCollection 2024 May.

Authors

Shi-Tao Zhao^{1

2}, Zhi-Cong Qiu^{1

2}, Rui-Yuan Zeng^{1

2}, Hua-Xi Zou³, Rong-Bin Qiu^{1

2}, Han-Zhi Peng^{1

2}, Lian-Fen Zhou^{1

2}, Zhi-Qiang Xu^{1

2}, Song-Qing Lai^{1

2}, Li Wan^{1

2}

Affiliations

¹ Department of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
² Institute of Cardiovascular Surgical Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
³ Department of Cardiovascular Surgery, The Second Affiliated Hospita, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330200, P.R. China.

Abstract

Ischemic cardiomyopathy (ICM) is a serious cardiac disease with a very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of the underlying pathological processes of cardiomyocyte injury is key to the development of cardioprotective strategies. Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides to lethal levels, resulting in oxidative damage to the cell membrane. The current understanding of the role and regulation of ferroptosis in ICM is still limited, especially in the absence of evidence from large-scale transcriptomic data. Through comprehensive bioinformatics analysis of human ICM transcriptome data obtained from the Gene Expression Omnibus database, the present study identified differentially expressed ferroptosis-related genes (DEFRGs) in ICM. Subsequently, their potential biological mechanisms and cross-talk were analyzed, and hub genes were identified by constructing protein-protein interaction networks. Ferroptosis features such as reactive oxygen species generation, changes in ferroptosis marker proteins, iron ion aggregation and lipid oxidation, were identified in the H9c2 anoxic reoxygenation injury model. Finally, the diagnostic ability of Gap junction alpha-1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha-synuclein (SNCA) were identified through receiver operating characteristic curves and the expression of DEFRGs was verified in an in vitro model. Furthermore, potential drugs (retinoic acid) that could regulate ICM ferroptosis were predicted based on key DEFRGs. The present article presents new insights into the role of ferroptosis in ICM, investigating the regulatory role of ferroptosis in the pathological process of ICM and advocating for ferroptosis as a potential novel therapeutic target for ICM based on evidence from the ICM transcriptome.

Keywords: bioinformatics; database; ferroptosis; heart transcriptome; ischemic cardiomyopathy.

Grants and funding

Funding: The present study was supported by the National Nature Science Foundation of China (grant nos. 81860082 and 82160073) and Jiangxi Provincial Natural Science Foundation (grant nos. 20212ACB206011, 20224ACB206002 and 20232BAB206009).