Analysis of time series gene expression and DNA methylation reveals the molecular features of myocardial infarction progression (RNA-Seq)

Myocardial infarction (MI) is one of the deadliest diseases in the world, and the changes at the molecular level after MI and the DNA methylation features are not clear. Understanding the molecular characteristics of the early stages of MI is of significance for the treatment of the disease. In this study, RNA-seq and MeDIP-seq were performed on heart tissue from mouse models at multiple time points (0 h, 10 min,1 h, 6 h, 24 h and 72 h) to explore genetic and epigenetic features that influence MI progression. Analysis based on a single point in time, the number of differentially expressed genes (DEGs)and differentially methylated regions (DMRs)increased with the time of myocardial infarction, using 0 h as a control group. Moreover, within 10 minutes of MI onset, the cells are mainly in immune response, and as the duration of MI increases, apoptosis begins to occur. Analysis based on time series data, the expression of 1012 genes was specifically downregulated, and these genes were associated with energy metabolism. The expression of 5806 genes was specifically upregulated, and these genes were associated with immune regulation, inflammation and apoptosis. 14 transcription factors were identified in the genes involved in apoptosis and inflammation, which may be potential drug targets. Analysis based on MeDIP-seq combined with RNA-seq methodology, focused on methylation at the promoter region. GO revealed that the downregulated genes with hypermethylation at 72 h were enriched in biological processes such as cardiac muscle contraction. In addition, the upregulated genes with hypomethylation at 72 h were enriched in biological processes, such as cell-cell adhesion, regulation of the apoptotic signalling pathway and regulation of angiogenesis. Among these genes, the Tnni3 gene was also present in the downregulated model. Hypermethylation of Tnni3 at 72 hours after MI may be an important cause of exacerbation of MI. Eighteen 12-week-old male C57BL/6JR mice were included in the experiment. The experiment was divided into 6 groups. Each group contained 3 mice, 5 groups of which required surgery to make models, called the operation group, and the other group was the sham operation group (0 h). The operation group was divided into 10 min, 1 h, 6 h, 24 h and 72 h subgroups after MI. The mice were anaesthetized with sodium pentobarbital (50 mg/kg, intraperitoneally) and placed on the operating table. The mice in the surgery group were intubated, and the left anterior descending coronary artery was ligated to induce MI, separately. The mice in the control group received the same operation, sutured through the inferior artery, but not ligated. Complete anaesthesia of mice with 1-3% isoflurane after specific time of MI, followed by euthanasia by cervical dislocation. Total RNA was isolated from myocardial region of infarcted left ventricle.