Conclusions
Our findings profiled the molecular variations from the perspective of DNA methylation in the early stage of AMI and provided promising epigenetic-based biomarkers for the early clinical diagnosis and therapeutic targets of AMI.
Results
We used the RNA-seq and MeDIP-seq on heart tissues from AMI mouse models at series of time points (Sham, AMI 10-min, 1-h, 6-h, 24-h and 72-h), to comprehensively describe the transcriptome and genome-wide DNA methylation changes at above time points. We identified 18814, 18614, 23587, 26018 and 33788 differential methylation positions (DMPs) and 123, 135, 731, 1419 and 2779 differentially expressed genes (DEGs) at 10-min, 1-h, 6-h, 24-h and 72-h AMI, respectively, compared with the sham group. Remarkably, the 6-h AMI with the drastic changes of DEGs and a large number of enriched functional pathways in KEGG may be the most critical stage of AMI process. The 4, 9, 40, 26, and 183 genes were further identified at each time point, based on the negative correlation (P < 0.05) between the differential mRNA expression and the differential DNA methylation. The mRNA and the promoter methylation expressions of five genes (Ptpn6, Csf1r, Col6a1, Cyba, and Map3k14) were validated by qRT-PCR and BSP methods, and the mRNA expressions were further confirmed to be regulated by DNA methylation in cardiomyocytes in vitro. Conclusions: Our findings profiled the molecular variations from the perspective of DNA methylation in the early stage of AMI and provided promising epigenetic-based biomarkers for the early clinical diagnosis and therapeutic targets of AMI.