Abstract
Sepsis-induced cardiomyopathy (SIC), with a possibly reversible cardiac dysfunction, is a potential complication of septic shock. Despite quite a few mechanisms including the inflammatory mediator, exosomes, and mitochondrial dysfunction, having been confirmed in the existing research studies we still find it obscure about the overall situation of gene co-expression that how they can affect the pathological process of SIC. Thus, we intended to find out the crucial hub genes, biological signaling pathways, and infiltration of immunocytes underlying SIC. It was weighted gene co-expression network analysis that worked as our major method on the ground of the gene expression profiles: hearts of those who died from sepsis were compared to hearts donated by non-failing humans which could not be transplanted for technical reasons (GSE79962). The top 25 percent of variant genes were abstracted to identify 10 co-expression modules. In these modules, brown and green modules showed the strongest negative and positive correlation with SIC, which were primarily enriched in the bioenergy metabolism, immunoreaction, and cell death. Next, nine genes (LRRC39, COQ10A, FSD2, PPP1R3A, TNFRSF11B, IL1RAP, DGKD, POR, and THBS1) including two downregulated and seven upregulated genes which were chosen as hub genes that meant the expressive level of which was higher than the counterparts in control groups. Then, the gene set enrichment analysis (GSEA) demonstrated a close relationship of hub genes to the cardiac metabolism and the necroptosis and apoptosis of cells in SIC. Concerning immune cells infiltration, a higher level of neutrophils and B cells native and a lower level of mast cells resting and plasma cells had been observed in patients with SIC. In general, nine candidate biomarkers were authenticated as a reliable signature for deeper exploration of basic and clinical research studies on SIC.
Highlights
Due to a ununiform definition of sepsis and different mechanisms of disease reporting, the precise incidence data of sepsis remain vague
It was shown in the KEGG pathway that oxidative phosphorylation, diabetic cardiomyopathy, and fatty acid degradation were the primarily enriched pathways in the brown module (Figure 3A)
The top 10 KEGG pathways were enriched in the rap1 signaling pathway and apoptosis (Figure 3C), while the leading parts demonstrated by the GO terms were actin-binding, cell-substrate junction, focal adhesion and regulation of apoptotic signaling pathway, etc. (Figure 3D)
Summary
Due to a ununiform definition of sepsis and different mechanisms of disease reporting, the precise incidence data of sepsis remain vague. Those data are mainly obtained from developed countries with a result showing 2.8 million deaths per year caused by sepsis (Cecconi et al, 2018). Many pieces of evidence have shown that the ventricular myocardium is suppressed with a characteristic of diastolic cardiac dysfunction during the occurrence of sepsis (Kakihana et al, 2016). Details about gene co-expression related to the pathological process of SIC remain unclear. Elucidating the underlying genes correlated to SIC may be instrumental for in-depth biological and clinical research studies
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