Identifying Immune Cell Infiltration and Hub Genes During the Myocardial Remodeling Process After Myocardial Infarction

Abstract

Purpose

Myocardial remodeling after myocardial infarction (MI) is a complex repair process following myocardial injury, characterized by the infiltration of multiple types of immune cells. However, the underlying molecular mechanism of myocardial remodeling after MI remains obscure. This study aimed to identify the hub differential expression genes (DEGs) of myocardial remodeling after MI and determine the distribution of immune cells infiltrating the pathology.

Methods

We downloaded GSE132143, GSE151834, and GSE176092 data from the GEO database. The GSE132143 dataset was used to identify DEGs, perform functional annotation, and screen hub genes based on protein-protein interaction (PPI) analysis. The GSE151834 dataset was used to validate the expression of hub genes. CIBERSORTx analysis was performed to explore the immune microenvironment in myocardial remodeling after MI. After conducting a literature review, we selected P3H3 to confirm the expression by utilizing immunohistochemistry and qRT-PCR. Finally, the snRNA-seq data in dataset GSE176092 was used for clarifying the expression of these hub genes in various cell clusters.

Results

We found 975 DEGs in myocardial remodeling after MI. Four hub genes (P3H3, COL15A1, COL16A1, COL27A1) were identified and were verified in the GSE151834 dataset. According to immune infiltration analysis, CD4+ naive T cells, regulatory T cells, monocytes, M2 macrophages, and neutrophils were involved in the pathological process of myocardial remodeling after MI. Additionally, in vitro experiments verified that P3h3 expression was significantly elevated in myocardial remodeling after MI. The snRNA-seq data analyzed that P3h3, Col15a1, Col16a1, and Col27a1 were highly expressed in fibroblasts of post-MI.

Conclusion

This study identified four hub genes P3H3, COL15A1, COL16A1, and COL27A1, particularly P3H3, as potential targets for targeted therapy in MI patients.

Keywords:

• myocardial infarction
• myocardial remodeling
• hub genes
• immune infiltration
• bioinformatic analysis

Data Sharing Statement

The data of bioinformatics analysis (GSE132143, GSE151834, and GSE176092) for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/). Further inquiries can be directed to the corresponding author.

Ethics Statement

All animal experiments were approved by the Institutional Animal Care and Use Committee of Shanghai General Hospital (NO.2023AW004) and followed the standards of the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Acknowledgments

The authors would like to thank Dr. Win Topatana from Zhejiang University for the revision of this manuscript.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (No. 81470471), and the Natural Science Foundation of Shanghai (No. 19ZR11440600).