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Characterization of Circular RNA and microRNA Profiles in Septic Myocardial Depression: a Lipopolysaccharide-Induced Rat Septic Shock Model

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Abstract

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.

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Acknowledgments

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.

Funding

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).

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  1. Tie-Ning Zhang and Ni Yang authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, PICU, Shengjing Hospital of China Medical University, No.36, SanHao Street, Shenyang City, Liaoning Province, 110004, People’s Republic of China

    Tie-Ning Zhang, Ni Yang, Jing Xia, Ri Wen, Tao Zhang, Wen-Liang Song & Chun-Feng Liu

  2. Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA

    Julie E. Goodwin, Kali Mahrer & Han Zhou

  3. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China

    Da Li

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  1. Tie-Ning Zhang
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Electronic supplementary material

ESM 1

(PDF 225 kb)

Supplementary Figure 1

The density distribution of circRNAs in each chromosome of every heart sample. (PDF 6534 kb)

Supplementary Figure 2

The length distribution of miRNAs in each heart sample. (PDF 2962 kb)

Supplementary Figure 3

The density distribution of miRNAs in each chromosome of every heart sample. (PDF 11119 kb)

Supplementary Figure 4

The first nucleotides bias of known miRNA in each heart sample. (PDF 6966 kb)

Supplementary Figure 5

The first nucleotides bias of novel miRNA in each heart sample. (PDF 5539 kb)

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Zhang, TN., Yang, N., Goodwin, J.E. et al. Characterization of Circular RNA and microRNA Profiles in Septic Myocardial Depression: a Lipopolysaccharide-Induced Rat Septic Shock Model. Inflammation 42, 1990–2002 (2019). https://doi.org/10.1007/s10753-019-01060-8

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