Ferroptosis and autophagy-related genes contribute to hypertrophic cardiomyopathy progression

铁死亡和自噬相关基因促进肥厚型心肌病进展

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Abstract

We aimed to investigate the ferroptosis- and autophagy-related differentially expressed genes (DEGs) that might be potential targets for hypertrophic cardiomyopathy (HCM) progression.GSE89714 and ferroptosis- and autophagy databases were utilized to obtain the overlapping ferroptosis- and autophagy-related DEGs. Enrichment pathway analysis was performed and the hub genes were obtained. The HCM mice model, macrophage cell Line and single-cell sequencing data were used to validate the hub genes. Utilizing the Limma package and Venn diagram, 25 ferroptosis-related and 47 autophagy-related DEGs were obtained. They were mainly enriched in autophagy, ferroptosis, neurodegeneration pathways, multiple diseases, processes utilizing autophagic mechanisms, hijacked molecular function, and antioxidant activity. In the protein-protein interaction network, the hub DEGs, including BCL2L1, CD44, IGF1, CDKN1B, APP, CTNNB1, HMGB1, LAMP1, TFRC, and CXCR4 were obtained. Using a single-cell portal, sequencing of hub gene expression demonstrated that the hub genes were highly expressed in macrophages in the human and HCM hearts. The screened hub genes, BCL2L1, CD44, IGF1, CDKN1B, APP, CTNNB1, HMGB1, LAMP1, TFRC, and CXCR4, may be therapeutic targets for diagnosing HCM and its progression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-19206-0.

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