Identification and verification of immune-related biomarkers and immune infiltration in diabetic heart failure

Zuoquan Zhong; Hanlin Zhang; Ting Xu; Jinjin Hao; Xing Chen; Shimin Sun; Jinjin Yang; Jing Sun; Hui Lin; Hangyuan Guo

doi:10.3389/fcvm.2022.931066

Identification and verification of immune-related biomarkers and immune infiltration in diabetic heart failure

Front Cardiovasc Med. 2022 Nov 17:9:931066. doi: 10.3389/fcvm.2022.931066. eCollection 2022.

Authors

Zuoquan Zhong¹, Hanlin Zhang², Ting Xu³, Jinjin Hao³, Xing Chen⁴, Shimin Sun², Jinjin Yang³, Jing Sun², Hui Lin⁵, Hangyuan Guo^{1

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Affiliations

¹ Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, China.
² The First Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, China.
³ Department of Cardiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁴ Department of Respiratory Medicine, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, China.
⁵ Department of Cardiovascular, Lihuili Hospital Affiliated to Ningbo University, Ningbo, Zhejiang, China.
⁶ College of Medicine, Shaoxing University, Shaoxing, Zhejiang, China.
⁷ Shaoxing People's Hospital, Shaoxing Key Laboratory of Cardio-Cerebral Vascular Disease Rehabilitation Technology Research, Shaoxing, Zhejiang, China.

Abstract

Purpose: Diabetic heart failure (DHF) or cardiomyopathy is a common complication of diabetes; however, the underlying mechanism is not clear. In the present study, the authors searched for differentially expressed genes associated with DHF and the molecular types of immune cells based on bioinformatics.

Methods: The RNA expression dataset of DHF was obtained from the NCBI Gene Expression Omnibus (GEO) database. After preprocessing the data, the differentially expressed genes (DEGs) between the DHF group and the non-diabetic heart failure (NHF) group were screened and intersected with immune-related genes (IRGs) in the ImmPort database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID tool. The ssGSEA algorithm was used to evaluate immune infiltration of the heart tissue in each group. In addition, the protein-protein interaction (PPI) network and miRNA-mRNA network were constructed using the STRING online website and Cytoscape program. Finally, validation analysis was performed using animal models.

Results: Eight immune-related core genes were identified. GO and KEGG showed that core genes were mainly enriched in angiogenesis and cytokine-cytokine receptor interaction. Immune infiltration results showed that activated dendritic cells, central memory CD4 T cells, central memory CD8 T cells, myeloid-derived suppressor cells (MDSCs), neutrophils, and regulatory T cells may be involved in DHF. Neutrophils may play a key role in the pathogenesis of HF in diabetes.

Conclusion: Immune-related core genes and immune infiltrating cells provide a new perspective on the pathogenesis of DHF.

Keywords: bioinformatics; cardiac function; diabetic cardiomyopathy; diabetic heart failure; immunomodulation.