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Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy
Zhou Liu1, Ying-Nan Song2, Kai-Yuan Chen2
1School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, Guizhou Province, China.
Insights
Dilated cardiomyopathy (DCM) involves collagen genes COL1A2 and COL3A1, and microRNAs hsa-miR-5682 and hsa-miR-4500. These are linked to the IL-17 signaling pathway and inflammation, offering insights into DCM pathogenesis.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Immunology
Background:
- Dilated cardiomyopathy (DCM) is a leading cause of heart failure, characterized by ventricular dilation and impaired contractility.
- DCM pathogenesis involves cytoskeletal proteins, mitochondrial dysfunction, microvascular changes, and fibrosis.
- Understanding DCM's molecular underpinnings and identifying biomarkers are crucial for managing this global health burden.
Purpose of the Study:
- To identify candidate genes and molecular pathways implicated in the development of dilated cardiomyopathy (DCM).
- To explore potential microRNA (miRNA) regulatory networks and immune cell infiltration patterns in DCM patients.
Main Methods:
- Differential gene expression analysis of two independent DCM patient datasets (GSE3585, GSE5406).
- Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and pathway enrichment analyses.
- Protein-protein interaction (PPI) network construction, miRNA target prediction, and immune cell infiltration analysis (CIBERSORT).
Main Results:
- Identified 97 differentially expressed genes (DEGs) in DCM patients, enriched in extracellular matrix and IL-17 signaling pathways.
- The PPI network highlighted COL3A1 and COL1A2 as key genes in DCM pathogenesis.
- hsa-miR-5682 and hsa-miR-4500 were predicted to target COL3A1 and COL1A2, suggesting a regulatory role.
Conclusions:
- COL1A2 and COL3A1, along with their targeting miRNAs (hsa-miR-5682, hsa-miR-4500), are potentially critical in DCM pathogenesis.
- These findings link DCM to the IL-17 signaling pathway and acute inflammatory responses.
- The study provides potential diagnostic and therapeutic targets for dilated cardiomyopathy.
Background:
Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated.
Aim:
To investigate the candidate genes and pathways involved in DCM patients.
Methods:
Two expression datasets (GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between the DCM patients and healthy individuals were identified using the R package "linear models for microarray data." The pathways with common DEGs were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network (PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs (miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT.
Results:
In total, 97 DEGs (47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in "response to growth factor," "extracellular matrix," and "extracellular matrix structural constituent." KEGG pathway analysis indicated that the DEGs were mainly enriched in "protein digestion and absorption" and "interleukin 17 (IL-17) signaling pathway." The PPI network suggested that collagen type III alpha 1 chain (COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells.
Conclusion:
COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM.
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