Identified Three Interferon Induced Proteins as Novel Biomarkers of Human Ischemic Cardiomyopathy.

Cheng Chen,Wenyong Xiong,Shubai Liu,Jiao Tian,Zhicheng He,Yingying He

doi:10.3390/ijms222313116

Abstract

Ischemic cardiomyopathy is the most frequent type of heart disease, and it is a major cause of myocardial infarction (MI) and heart failure (HF), both of which require expensive medical treatment. Precise biomarkers and therapy targets must be developed to enhance improve diagnosis and treatment. In this study, the transcriptional profiles of 313 patients’ left ventricle biopsies were obtained from the PubMed database, and functional genes that were significantly related to ischemic cardiomyopathy were screened using the Weighted Gene Co-Expression Network Analysis and protein–protein interaction (PPI) networks enrichment analysis. The rat myocardial infarction model was developed to validate these findings. Finally, the putative signature genes were blasted through the common Cardiovascular Disease Knowledge Portal to explore if they were associated with cardiovascular disorder. Three interferon stimulated genes (IFIT2, IFIT3 and IFI44L), as well as key pathways, have been identified as potential biomarkers and therapeutic targets for ischemic cardiomyopathy, and their alternations or mutations have been proven to be strongly linked to cardiac disorders. These novel signature genes could be utilized as bio-markers or potential therapeutic objectives in precise clinical diagnosis and treatment of ischemic cardiomyopathy.

Highlights

Accepted: 15 November 2021Ischemic cardiomyopathy (ISCM) is a symptom in which blood flow to heart is reduced or stopped, resulting in heart muscle injury [1]
Combined with the Eigengene dendrogram analysis and the module–trait relationship correlation results, the green module was clustered with ISCM tightly (Figure 2A, Supplementary Table S2) and the contained genes has the strongest correlation with ISCM status (Figure 2A,B)
The scatter plot of MM was plotted against the Genes Significance (GS) in each significant module, with each point representing a gene contained in a module (Supplementary Figure S2)

Summary

Introduction

Ischemic cardiomyopathy (ISCM) is a symptom in which blood flow to heart is reduced or stopped, resulting in heart muscle injury [1]. This persistent ISCM is the most prevalent cause of heart failure (HF) and a leading cause of death worldwide. IFIT (IFN-induced proteins with Tetratricopeptide Repeat (TPR) motifs) family proteins bind eiF3C or eiF3E to inhibit translation initiation pathogens, including IFIT1/1B, IFIT2, IFIT3 and IFIT5 in human and six members in murine (IFIT1/1B/1C, IFIT2, IFIT3/3B), and target viral protein production through a variety of mechanisms [7]. Multiple TPR domains is thought to confer a wide range of effects on cellular and viral functions, including transcription and translation regulation, anti-proliferative

Objectives

Methods

Results

Conclusion