Identification of potential molecular mechanisms and small molecule drugs in myocardial ischemia/reperfusion injury

Abstract

Myocardial ischemia/reperfusion (MI/R) injury is a complex phenomenon that causes severe damage to the myocardium. However, the potential molecular mechanisms of MI/R injury have not been fully clarified. We identified potential molecular mechanisms and therapeutic targets in MI/R injury through analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were found between MI/R injury and normal samples, and overlapping DEGs were found between GSE61592 and GSE67308. Gene Ontology (GO) and pathway analysis were performed for overlapping DEGs by Database for Annotation, Visualization and Integration Discovery (DAVID). Then, a network of protein-protein interaction (PPI) was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) database. Potential microRNAs (miRNAs) and therapeutic small molecules were screened out using microRNA.org database and the Comparative Toxicogenomics database (CTD), respectively. Finally, we identified 21 overlapping DEGs related to MI/R injury. These DEGs were significantly enriched in IL-17 signaling pathway, cytosolic DNA-sensing pathway, chemokine signaling, and cytokine-cytokine receptor interaction pathway. According to the degree in the PPI network, CCL2, LCN2, HP, CCL7, HMOX1, CCL4, and S100A8 were found to be hub genes. Furthermore, we identified potential miRNAs (miR-24-3p, miR-26b-5p, miR-2861, miR-217, miR-4251, and miR-124-3p) and therapeutic small molecules like ozone, troglitazone, rosiglitazone, and n-3 polyunsaturated fatty acids for MI/R injury. These results identified hub genes and potential small molecule drugs, which could contribute to the understanding of molecular mechanisms and treatment for MI/R injury.

Ozone Activates the Nrf2 Pathway and Improves Preservation of Explanted Adipose Tissue In Vitro

“…It has been already demonstrated in different cell types [ 7 , 20 , 29 ] that mild O 3 treatment leads to a specific antioxidant response by inducing gene transcription via AREs. By combining sub-nuclear tracking of Nrf2 localization at fluorescence and electron microscopy and functional genetic engineering approaches, it was demonstrated that low O 3 concentrations such as 10 and 20 μg increase Nrf2 protein stability by preventing its Keap1-mediated degradation [ 7 , 30 ].…”

“…In particular, concentrations of 10 and 16 μg O 3 were found to induce genes involved in the cellular response to stress (Hmox1, ERCC4, CDKN1A) and in the transcription machinery (CTDSP1). Finally, a recent microarray analysis of gene expression correlated the expression of Hmox1 gene with the therapeutic use of O 3 in myocardial ischemia/reperfusion injury [ 29 ]. It is therefore well established that the O 3 -mediated activation of Nrf2 induces the transcription of antioxidant genes.…”