Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression

Abstract

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, 6, 24, 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 min 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. Fourteen 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 signaling pathway and regulation of angiogenesis. Among these genes, the Tnni3 gene was also present in the downregulated model. Hypermethylation of Tnni3 at 72 h after MI may be an important cause of exacerbation of MI.

Zinc Finger Proteins in the War on Gastric Cancer: Molecular Mechanism and Clinical Potential

“…As a wide-ranging family of eukaryotic transcription variables, ZFPs have exhibited promising potential in several biological fields, such as disease treatment, on account of their specific transcriptional regulation roles [204]. GC remains one of the most prevalent malignancies worldwide, and notwithstanding remarkable breakthroughs in current therapies for GC, such as surgery, chemoradiotherapy and immunotherapy, its prognosis, particularly regarding long-term viability, remains unsatisfactory [205].…”

A review on regulation of DNA methylation during post-myocardial infarction

“…Currently, medications such as aspirin, warfarin, tissue plasminogen activator, and interventional therapy, such as percutaneous coronary intervention (PCI), are the mainstay of treatment for AMI ( Lu et al, 2015 ; Doenst et al, 2019 ; Sabatine and Braunwald, 2021 ). However, unpredictable complications such as bleeding, ischemia/reperfusion injury, and coronary restenosis may occur, highlighting the need for safer and more innovative therapeutic strategies to optimize clinical outcomes ( McCarthy et al, 2018 ; Doenst et al, 2019 ; Mackman et al, 2020 ; Zhang et al, 2022 ).Several studies have observed significant individual methylation differences in patients with MI ( Ek et al, 2016 ; Rask-Andersen et al, 2016 ; Thunders et al, 2019 ; Han et al, 2022 ; Luo et al, 2022 ; Ren et al, 2022 ). Further exploration of the regulatory mechanisms of DNA methylation and its potential impact on metabolism and vascular physiology after MI may help reduce the incidence of post-MI complications ( Ward-Caviness et al, 2018 ).…”

“…Research has demonstrated alterations in the degree of methylation of certain genes in individuals with myocardial infarction ( Ek et al, 2016 ; Rask-Andersen et al, 2016 ; Ward-Caviness et al, 2018 ; Thunders et al, 2019 ), which are associated with cardiac function, cardiogenesis, and recovery after ischemic injury. To understand the early dynamic changes of gene expression after MI, RNA-seq and MeDIP-seq were used on heart tissues from AMI mice at different time points ( Han et al, 2022 ; Luo et al, 2022 ), and the results showed that DNA methylation plays an important role in the pathophysiological progression after MI. We reviewed the existing research and elucidated the role of DNA methylation regulation in inflammation, fibrosis and other aspects after myocardial infarction.…”

From multi-omics approaches to personalized medicine in myocardial infarction

“…Genetic mutations could render individuals more susceptible to cardiac ailments, thereby amplifying the risk of MI ( 304 ). In parallel, aberrant gene expression could disrupt the functionality of the cardiovascular system, further hastening the onset of MI ( 305 , 306 ). However, beyond genetics, subsequent alterations could serve as triggers for MI, encompassing factors such as environmental influences, lifestyles, and epigenetics ( 123 , 307 – 310 ).…”