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Updated: Sep 12, 2025
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Identification of marker genes associated with oxidative stress in hypertrophic cardiomyopathy using bioinformatics
Jian Zhuo1, Ding Ding2, Mengkang Fan3
1Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China. 1931320060@stmail.ntu.edu.cn.
Insights
This study identifies seven key oxidative stress genes contributing to hypertrophic cardiomyopathy (HCM). These genes are linked to apoptosis and immune responses, offering new insights into HCM development.
Area of Science:
- Cardiovascular Genetics
- Molecular Biology
- Bioinformatics
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent inherited heart condition.
- The precise role of oxidative stress in HCM pathogenesis remains incompletely understood.
Purpose of the Study:
- To identify and characterize oxidative stress-related genes associated with HCM.
- To elucidate the functional significance of these genes in HCM development using bioinformatic approaches.
Main Methods:
- Bioinformatic analysis of public gene expression datasets (GSE36961, GSE141910).
- Identification of oxidative stress-related differentially expressed genes (OS-DEGs) using LASSO and SVM-RFE algorithms.
- Functional enrichment analyses (GO, pathway, GSEA) and immune cell infiltration analysis (CIBERSORT).
- In vitro validation in neonatal rat cardiomyocytes.
Main Results:
- 33 OS-DEGs linked to HCM were identified, primarily associated with apoptosis and immune response.
- Seven marker genes (JAK2, EDNRA, KCNA5, DNAJC15, CA3, PRKCD, KLF2) were pinpointed.
- Functional analysis indicated these markers regulate oxidative stress, immune responses, and cytokine interactions in HCM.
- In vitro studies confirmed elevated oxidative stress and apoptosis in HCM models.
Conclusions:
- This study identified seven novel oxidative stress-related genes implicated in HCM pathogenesis.
- Oxidative stress likely contributes to HCM through apoptosis and modulation of immune responses.
- PRKCD and EDNRA may influence the immune microenvironment in HCM patients.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiomyopathy, and the mechanisms by which oxidative stress contributes to HCM remain unclear. This study aimed to identify HCM-associated oxidative stress genes and evaluate their significance in HCM pathogenesis through bioinformatic analysis of public datasets. GSE36961 and GSE141910 were downloaded from the Gene expression Omnibus (GEO) database, and genes associated with oxidative stress were searched in the Gene Ontology (GO) database. After differential analysis, marker genes were obtained using LASSO and SVM-RFE algorithms. DAVID was used, along with the GSVA and GSEA packages to perform gene ontology, pathway function enrichment, and gene set enrichment analyses. CIBERSORT was used to analyze immune cell infiltration. Subsequently, validation of these genes was performed using the GSE141910 dataset. Finally, we validated gene expression and levels of oxidative stress in cellular models. In total, 33 OS-DEGs related to HCM were identified. These were closely related to apoptosis and immune response. Subsequently, seven marker genes from OS-DEGs were identified: JAK2, EDNRA, KCNA5, DNAJC15, CA3, PRKCD and KLF2. The functional enrichment analysis suggested that these markers may play corresponding roles in HCM by regulating oxidative stress, immune responses, cytokine interactions, and multiple other processes. In addition, according to CIBERSORT analysis, PRKCD and EDNRA may have an effect on the immune microenvironment of HCM patients. In vitro studies using neonatal rat cardiomyocytes showed increased ROS production and caspase activation, suggesting elevated oxidative stress and apoptosis in HCM. This study identified 7 oxidative stress-related genes in HCM, and deeply analyzed the function and regulation of the marker genes. At the same time, we also proposed that oxidative stress participate in HCM through apoptosis.
