Integrated RNA- and miRNA-sequencing analysis identifies molecular basis for stress-induced heart injury in mouse models

Abstract

Background: Work stress and its contribution to cardiovascular diseases are well documented in recent years, but its molecular mechanisms are still not clear. In this study, we aimed to explore the potential pathophysiological mechanisms of stress-induced heart injury in mouse models. Methods: The RNA-and miRNA-sequencing profiles from five stress-treated mice and five control mice were performed. After normalization, differentially expressed genes (DEGs) and miRNAs (DEmiRs) were identified using the edgeR method. Then, based on the functional enrichment analysis and protein-protein interaction (PPI) network, as well as miRNA-mRNA interactome, the core DEGs and DEmiRs associated with stress-induced heart injury were marked and validated by qPCR, and the DEmiR targets were validated in vitro. Results: A total of 293 genes and 29 miRNAs were identified as DEGs and DEmiRs respectively, and Alb, Stat1, C3, Irf7, Usp18 were hub genes in the PPI network. The enrichment pathways were related to inflammation and immune, coagulation, oxidative phosphorylation, vascular development, cell cycle and extracellular matrix (ECM), which likely mediated the biological injury processes or reflected the results of damage. The target DEGs of DEmiRs were clustered in angiogenesis, immune system process and ECM. After the validation in vitro, we found that miR-29b-3p mimics could down-regulate the expression of its predicted targets, Pxdn and Col15a1. Conclusions: The findings revealed a molecular basis from the gene and miRNA level for the heart injury associated with stress. miR-29b-3p, as a potential target to repair stress-induced ECM disorder in heart, deserves further study.