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

Int J Mol Sci. 2021 Dec 4;22(23):13116. 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.

Keywords: IFIT2/3; WGCNA; heart failure; interferon stimulated genes; ischemic cardiomyopathy.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics*
  • Biomarkers
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / pathology
  • Disease Models, Animal
  • Gene Regulatory Networks
  • Heart Ventricles / pathology
  • Humans
  • Interferons / genetics*
  • Interferons / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Metoprolol / pharmacology
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / physiopathology
  • Myocardial Ischemia / genetics
  • Myocytes, Cardiac / pathology
  • Protein Interaction Maps / genetics
  • RNA-Binding Proteins / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Suppressor Proteins / genetics*
  • Ventricular Function, Left

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers
  • IFI44L protein, human
  • IFIT2 protein, human
  • IFIT3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • RNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Interferons
  • Metoprolol