Characterization of Long Noncoding RNA and mRNA Profiles in Sepsis-Induced Myocardial Depression

Abstract

Septic shock with heart dysfunction is very common in intensive care units. However, whether long noncoding RNA (lncRNA) and mRNA profiles differ between patients with and without myocardial depression is unknown. We generated rat models of hypodynamic septic shock induced by lipopolysaccharide. A total of 12 rat models was constructed and heart tissue from each was collected. Whole genomic RNA sequencing was performed on left ventricular tissue; 6,508 novel lncRNAs and 432 annotated lncRNAs were identified in heart samples, and 74 lncRNAs were expressed differently in the sepsis and control groups. Gene ontology term enrichment indicated apoptosis and its related pathways showed obvious enrichment, which suggested cell apoptosis could play a critical role in the process of myocardial depression. Furthermore, we focused on one lncRNA from the Pvt1 gene. By silencing this lncRNA, we demonstrated knockdown of Pvt1 expression could induce cell apoptosis in lipopolysaccharide-induced heart cells, through increasing the expression of c-Myc, Bid, Bax, and caspase-3 and decreasing the expression of Myd88 and Bcl-2, thereby proving its functional role in myocardial depression. These results demonstrate that lncRNAs both participate in and mediate the pathological process of myocardial depression. Our study improves the understanding of the basic molecular mechanisms underlying myocardial depression. Keywords: sepsis, lncRNA, myocardial depression, transcriptome, Pvt1