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Long non-coding RNA and mRNA expression profiles in rats with LPS-induced myocardial dysfunction

ABSTRACT: Sepsis is a life-threatening disease that often causes multiple organ dysfunctions. Long noncoding RNAs (lncRNAs) are involved in the pathogenesis and development of sepsis. However, there is little known about the function of lncRNAs in sepsis-induced myocardial dysfunction.To test the hypothesis that dysregulating lncRNAs may be involved in sepsis-induced myocardial dysfunction, we identified differentially expressed (DE) lncRNAs and mRNAs in cardiac tissue by high-throughput sequencing. We constructed coding and non-coding co-expression (CNC) and lncRNA-micro RNA (miRNA)-mRNA competing endogenous networks. The findings will provide useful information for exploring therapeutic candidate targets and new molecular biomarkers of septic myocardial injury.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE153086 | GEO | 2023/05/17

REPOSITORIES: GEO

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Project description:Background: Sepsis can lead to multiple organ damage, and the heart is one of the most vulnerable organs. Vagal nerve stimulation can reduce myocardial injury in sepsis and improve survival rate. However, the relative effect of disparate cell populations on sepsis induced myocardial dysfunction and the low-level tragus stimulation on it, remain unclear. Methods: We used the cardiac single-cell transcriptomic strategy to characterize the cardiac cell population and the network of cells that forms the heart. And we selected all cardiac macrophage from CD45+ cells using single-cell mRNA sequencing data. Then we used echocardiography performing, western blot and immunofluorescence and immunohistochemical technology to verify the data of the single-cell mRNA sequencing results. Results: In single-cell mRNA sequencing data, our analysis provides a comprehensive map of the cardiac cellular landscape uncovering multiple cell populations that contribute to sepsis induced myocardial dysfunction under low-level tragus stimulation. Pseudo timing analysis in single-cell sequencing showed that low level vagal nerve stimulation could induce the transformation of cardiac monocytes into M2 macrophages and play an anti-inflammatory role. After low-level tragus stimulation, the expression of α7nAChR in the heart tissue increased significantly. Echocardiography showed that low-level tragus stimulation could improve the cardiac function of septic myocardial injury of the mice. Comparing with the sepsis group, the expression of interleukin-1β in heart tissue of the mice in sepsis with low-level tragus stimulation group is significantly lower. Conclusion: Low-level tragus stimulation can improve sepsis-induced myocardial dysfunction by promoting cardiac monocytes to M2 macrophages. Goal of the study: In the present study, we aimed to screen macrophages, their crosstalk with other cells, and macrophages associated with cardiac injury and further verify their origins and roles in the septic myocardial injury process and low-level tragus stimulation (LL-TS) to treat septic myocardial dysfunction.

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Long non-coding RNA and mRNA expression profiles in rats with LPS-induced myocardial dysfunction

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