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. 2022 Feb 24:9:824756.
doi: 10.3389/fcvm.2022.824756. eCollection 2022.

Exploring the Communal Pathogenesis, Ferroptosis Mechanism, and Potential Therapeutic Targets of Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy via a Microarray Data Analysis

Zuoxiang Wang  1   2 , Qingyue Xia  3 , Wenxing Su  4 , Mingqiang Cao  1 , Yunjuan Sun  1 , Mingyang Zhang  1   2 , Weixiang Chen  1 , Tingbo Jiang  1
Affiliations

Exploring the Communal Pathogenesis, Ferroptosis Mechanism, and Potential Therapeutic Targets of Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy via a Microarray Data Analysis

Zuoxiang Wang et al. Front Cardiovasc Med. .

Abstract

Background: Cardiomyopathies are a heterogeneous group of heart diseases that can gradually cause severe heart failure. In particular, dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are the two main types of cardiomyopathies, yet the independent and communal biological mechanisms of both remain far from elucidated. Meanwhile, ferroptosis is a non-apoptotic form of cell death that has been proven to be associated with cardiomyopathies, but the concrete nature of the interaction remains unclear. Hence, this study explored the pathogenesis and ferroptosis mechanism of HCM and DCM via a bioinformatics analysis.

Methods: Six datasets were downloaded from the Gene Expression Omnibus (GEO) database based on the study inclusion/exclusion criteria. After screening the differentially expressed genes (DEGs) and hub genes of HCM and DCM, subsequent analyses, including functional annotation, co-expression, validation, and transcription factors (TF)-mRNA-microRNA (miRNA) regulatory network construction, were performed. In addition, ferroptosis-related DEGs were also identified and verified in HCM and DCM.

Results: We found 171 independent DEGs of HCM mainly enriched in the regulation of ERK1 and ERK2 cascade, while 171 independent DEGs of DCM were significantly involved in cell adhesion. Meanwhile, 32 communal DEGs (26 upregulated genes and 6 downregulated genes) and 3 hub genes [periostin (POSTN), insulin-like growth factor-binding protein-5 (IGFBP5), and fibromodulin (FMOD)] were determined to be shared between HCM and DCM and the functional annotation of these genes highlighted the important position of growth hormone in HCM and DCM. Moreover, we identified activating transcription factor 3 (ATF3), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and solute carrier family 1 member 5 (SLC1A5) as ferroptosis-related genes in HCM and STAT3 as a ferroptosis-related gene in DCM.

Conclusion: The identified independent and communal DEGs contribute to uncover a potentially distinct and common mechanism of HCM and DCM and ferroptosis-related genes could provide us with a novel direction for exploration. In addition, 3 hub genes could be potential biomarkers or therapeutic targets in patients with cardiomyopathy.

Keywords: bioinformatics analysis; dilated cardiomyopathy; ferroptosis; heart failure; hub genes; hypertrophic cardiomyopathy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Research design flowchart.
Figure 2
Figure 2
Identification of gene-expression profiles in the 4 datasets. (A) Volcano plot of GSE36961 microarray data. (B) Volcano plot of GSE32453 microarray data. (C) Volcano plot of GSE21610 microarray data. (D) Volcano plot of GSE79962 microarray data.
Figure 3
Figure 3
(A) Venn diagram of the 108 communal upregulated differentially expressed genes (DEGs) in HCM. (B) Venn diagram of the 95 communal downregulated DEGs in hypertrophic cardiomyopathy (HCM). (C) Venn diagram of the 146 communal upregulated DEGs in dilated cardiomyopathy (DCM). (D) Venn diagram of the 57 communal downregulated DEGs in DCM. (E) Venn diagram of the 26 communal upregulated DEGs shared between HCM and DCM. (F) Venn diagram of the 6 communal downregulated DEGs shared between HCM and DCM.
Figure 4
Figure 4
(A) The functional annotation analysis of the communal DEGs by Metascape. (B) The pathway analysis of the communal DEGs by KOBAS version 3.0.
Figure 5
Figure 5
Protein–protein interaction (PPI) networks of the DEGs were constructed based on the STRING database and Cytoscape software. The red point represents upregulated genes and the blue point represents downregulated genes.
Figure 6
Figure 6
Three hub genes were screened by overlapping the top 5 genes found by the five algorithms of cytoHubba.
Figure 7
Figure 7
Hub genes and their co-expression genes were analyzed using GeneMANIA.
Figure 8
Figure 8
The expression levels of hub genes in GSE1145 and GSE3585. The comparison between the two sets of data used the mean t-test. P < 0.05 was considered to be statistically significant. HC, healthy control. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 9
Figure 9
The TF–mRNA–miRNA regulation network of hub genes was constructed using the MiRwalk and TRRUST databases.
Figure 10
Figure 10
(A) Venn diagram of preliminary ferroptosis-related DEGs in HCM. (B) Venn diagram of preliminary ferroptosis-related DEGs in DCM. (C) The expression levels of preliminary ferroptosis-related DEGs of HCM in GSE1145. (D) The expression levels of preliminary ferroptosis-related DEGs of DCM in GSE3585. *P < 0.05; **P < 0.01.
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References

    1. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al. . Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. (2006) 113:1807–16. 10.1161/CIRCULATIONAHA.106.174287 - DOI - PubMed
    1. Ciarambino T, Menna G, Sansone G, Giordano M. Cardiomyopathies: an overview. Int J Mol Sci. (2021) 22:7722. 10.3390/ijms22147722 - DOI - PMC - PubMed
    1. Waldmuller S, Erdmann J, Binner P, Gelbrich G, Pankuweit S, Geier C, et al. . Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure. Eur J Heart Fail. (2011) 13:1185–92. 10.1093/eurjhf/hfr074 - DOI - PubMed
    1. Jefferies JL, Towbin JA. Dilated cardiomyopathy. Lancet. (2010) 375:752–62. 10.1016/s0140-6736(09)62023-7 - DOI - PubMed
    1. Bos JM, Towbin JA, Ackerman MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing for hypertrophic cardiomyopathy. J Am Coll Cardiol. (2009) 54:201–11. 10.1016/j.jacc.2009.02.075 - DOI - PubMed