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

Yuru Han; Baoyu Duan; Jing Wu; Yanjun Zheng; Yinchen Gu; Xiaomeng Cai; Changlian Lu; Xubo Wu; Yanfei Li; Xuefeng Gu

doi:10.3389/fcvm.2022.912454

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

Front Cardiovasc Med. 2022 Jun 24:9:912454. doi: 10.3389/fcvm.2022.912454. eCollection 2022.

Authors

Yuru Han^{1

2}, Baoyu Duan¹, Jing Wu³, Yanjun Zheng¹, Yinchen Gu⁴, Xiaomeng Cai¹, Changlian Lu¹, Xubo Wu^{3

5}, Yanfei Li^{1

2}, Xuefeng Gu^{1

2

6}

Affiliations

¹ Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China.
² School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China.
³ School of Nursing, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ School of Basic Medical Sciences, Fudan University, Shanghai, China.
⁵ Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁶ School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, China.

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.

Keywords: DNA methylation; MeDIP-seq; RNA-seq; myocardial infarction; time series.