Characterization of Circular RNA and microRNA Profiles in Septic Myocardial Depression: a Lipopolysaccharide-Induced Rat Septic Shock Model
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Septic shock with heart dysfunction is common in intensive care units. However, the mechanism underlying myocardial depression is still unclear. Whether circular RNA (circRNA) or microRNA (miRNA) profiles differ between patients with and without myocardial depression is unknown. We generated a hypodynamic septic shock model induced by lipopolysaccharide (LPS) in adolescent rats. A total of 12 rats were utilized and heart tissue from each was collected. RNA sequencing was performed on left ventricular tissue. We focused on features of circRNAs and miRNAs, predicting their function by bioinformatic analysis and constructing circRNA-associated and miRNA-associated regulatory networks in heart tissue. We detected 851 circRNAs in heart samples, and 11 showed differential expression. A total of 639 annotated miRNAs and 91 novel miRNAs were explored including 78 showing differential expression between the two groups. We then constructed the most comprehensive circRNA-associated and miRNA-associated networks to explore their regulatory relationship in septic heart tissue, and demonstrated that different networks could potentially participate in and regulate the pathological process of sepsis. Furthermore, gene ontology term enrichment indicated miRNAs, and miRNA-mRNA networks could be associated with regulation and metabolic process, or influence cellular functions. The construction of regulator networks could improve the understanding of the basic molecular mechanisms underlying myocardial depression. It will be important for future investigations to ascertain the biological mechanisms present during the development of sepsis-induced myocardial depression to influence approaches to treatment.
KEY WORDScircular RNA micro RNA sepsis regulatory network transcriptome
T.N.Z., N.Y., and C.F.L. conceived and designed the study. T.N.Z., T.Z., and W.L.S. performed animal models and heart tissue collection. T.N.Z., N.Y., J.G., K.M., D.L., J.X., R.W., H.Z., and C.F.L performed RNA-seq data analysis and interpretation. T.N.Z., N.Y., J.G., K.M., and C.F.L. wrote the manuscript. All the authors have read and approved the final manuscript. T.N.Z. and N.Y. contributed equally to this work.
This study was funded by the National Natural Science Foundation of China (No. 81372039), the Natural Science Foundation of Liaoning Province (No. 2017225003, No. 2018108001), and the Science and Technology Foundation of Shenyang (No. F13-220-9-38).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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