Key result
Bioinformatics analysis and in vitro validation identified eight key autophagy-related genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) with excellent diagnostic capability (AUC > 0.8) for septic cardiomyopathy.
Why the study?
Septic cardiomyopathy is associated with poor prognosis and unclear mechanisms, with limited understanding of the role of dysregulated autophagy in its pathogenesis.
This study identifies eight key autophagy-related genes in septic cardiomyopathy that may serve as biomarkers and therapeutic targets.
Answers are grounded in this paper and cite their sources.
May offer new targets in septic cardiomyopathy; animal data leaves open human validation.
Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autophagy in the pathogenesis of SCM remains limited and uncertain. Exploring the molecular mechanisms of disease based on the transcriptomes of human pathological samples may bring the closest insights. In this study, we analyzed the differential expression of autophagy-related genes in SCM based on the transcriptomes of human septic hearts, and further explored their potential crosstalk and functional pathways. Key functional module and hub genes were identified by constructing a protein-protein interaction network. Eight key genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) that regulate autophagy in SCM were identified after validation in a lipopolysaccharide (LPS)-induced H9c2 cardiomyoblast injury model, as well as the autophagic characteristic features. Furthermore, we found that key genes were associated with abnormal immune infiltration in septic hearts and have the potential to serve as biomarkers. Finally, we predicted drugs that may play a protective role in SCM by regulating autophagy based on our results. Our study provides evidence and new insights into the role of autophagy in SCM based on human septic heart transcriptomes, which would be of great benefit to reveal the molecular pathological mechanisms and explore the diagnostic and therapeutic targets for SCM.
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Zou et al. (2022) studied Septic cardiomyopathy (n=84). Sepsis vs. Non-failing donor hearts and healthy controls was evaluated on Diagnostic capability of key autophagy-related genes for septic cardiomyopathy. Bioinformatics analysis and in vitro validation identified eight key autophagy-related genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) with excellent diagnostic capability (AUC > 0.8) for septic cardiomyopathy.
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