Molecular Mechanism of Sevoflurane Preconditioning Based on Whole-transcriptome Sequencing of Lipopolysaccharide-induced Cardiac Dysfunction in Mice

Xie, Jiawei; Li, Hongmei; Li, Shuai; Li, Jianling; Li, Yalan

doi:10.1097/fjc.0000000000001259

Cited by 6 publications

(4 citation statements)

References 52 publications

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“…Zhang, Z et al reported that metastasisrepressing factor OTUD1 deubiquitinated SMAD7 at Lysine 220 and prevented its degradation [55]. In the field of cardiovascular research, Xie, J et al reported that OTUD1 might be the target of sevoflurane-induced cardio-protection [56]; Quttainah, M et al reported the upregulation of OTUD1 in a hypertrophic myocardium [57], which was consistent with the results of this study.…”

Section: Discussionsupporting

confidence: 90%

Identification of TGF-β-related genes in cardiac hypertrophy and heart failure based on single cell RNA sequencing

Huang

et al. 2023

Aging

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Background: Heart failure (HF) remains a huge medical burden worldwide. Pathological cardiac hypertrophy is one of the most significant phenotypes of HF. Several studies have reported that the TGF-β pathway plays a double-sided role in HF. Therefore, TGF-β-related genes (TRGs) may be potential therapeutic targets for cardiac hypertrophy and HF. However, the roles of TRGs in HF at the single-cell level remain unclear. Method: In this study, to analyze the expression pattern of TRGs during the progress of cardiac hypertrophy and HF, we used three public single-cell RNA sequencing datasets for HF (GSE161470, GSE145154, and GSE161153), one HF transcriptome data (GSE57338), and one hypertrophic cardiomyopathy transcriptome data (GSE141910). Weighted gene co-expression network analysis (WGCNA), functional enrichment analysis and machine learning algorithms were used to filter hub genes. Transverse aortic constriction mice model, CCK-8, wound healing assay, quantitative real-time PCR and western blotting were used to validate bioinformatics results. Results: We observed that cardiac fibroblasts (CFs) and endothelial cells showed high TGF-β activity during the progress of HF. Three modules (royalblue, brown4, and darkturquoize) were identified to be significantly associated with TRGs in HF. Six hub genes (TANC2, ADAMTS2, DYNLL1, MRC2, EGR1, and OTUD1) showed anomaly trend in cardiac hypertrophy. We further validated the regulation of the TGF-β-MYC-ADAMTS2 axis on CFs activation in vitro. Conclusions: This study identified six hub genes (TANC2, ADAMTS2, DYNLL1, MRC2, EGR1, and OTUD1) by integrating scRNA and transcriptome data. These six hub genes might be therapeutic targets for cardiac hypertrophy and HF.

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Section: Discussionsupporting

confidence: 90%

Identification of TGF-β-related genes in cardiac hypertrophy and heart failure based on single cell RNA sequencing

Huang

et al. 2023

Aging

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“…Using RNA-sequencing techniques, we can not only rapidly obtain RNA expression levels and the functional annotation of DEGs but also discover new transcripts and structural variations ( Zhao, 2019 ). To date, there have been hundreds of studies involving RNA-sequencing analysis that have been used to investigate the treatment and mechanism of septic myocardial injury ( Xie et al, 2022 ; Yan et al, 2022 ). In this study, 2,385 DEGs were identified, of which levels of 2,094 were upregulated and those of 291 were downregulated.…”

Section: Discussionmentioning

confidence: 99%

Integration of transcriptomic, proteomic, and metabolomic data to identify lncRNA rPvt1 associations in lipopolysaccharide-treated H9C2 cardiomyocytes

Zhang,

Wen,

Yang

et al. 2023

Front. Genet.

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Background: Recent evidence has shown that the long non-coding RNA (lncRNA) rPvt1 is elevated in septic myocardial tissues and that its knockdown attenuates sepsis-induced myocardial injury. However, the mechanism underlying the role of rPvt1 in septic myocardial dysfunction has not been elucidated.Methods: In this study, we performed transcriptomic, proteomic, and metabolomic assays and conducted an integrated multi-omics analysis to explore the association between rPvt1 and lipopolysaccharide (Lipopolysaccharide)-induced H9C2 cardiomyocyte injury. LncRNA rPvt1 silencing was achieved using a lentiviral transduction system.Results: Compared to those with the negative control, rPvt1 knockdown led to large changes in the transcriptome, proteome, and metabolome. Specifically, 2,385 differentially expressed genes (DEGs), 272 differentially abundant proteins and 75 differentially expressed metabolites (DEMs) were identified through each omics analysis, respectively. Gene Ontology functional annotation, Kyoto Encyclopedia of Genes and Genomes, Nr, eukaryotic orthologous groups, and Clusters of Orthologous Groups of Proteins pathway analyses were performed on these differentially expressed/abundant factors. The results suggested that mitochondrial energy metabolism might be closely related to the mechanism through which Pvt1 functions.Conclusion: These genes, proteins, metabolites, and their related dysregulated pathways could thus be promising targets for studies investigating the rPvt1-regluatory mechanisms involved in septic myocardial dysfunction, which is important for formulating novel strategies for the prevention, diagnosis and treatment of septic myocardial injury.

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“…The exclusion criteria were as follows: (1) inherited cardiomyopathy; (2) inherited metabolic diseases; (3) immunodeficiency; (4) diagnosed with mitochondrial diseases; (5) patients with neoplastic diseases; (6) congenital heart disease in those patients in the sepsis groups (with or without myocardial injuries); (7) current coronavirus disease 2019 infection; (8) pulmonary hypertension; (9) suspected viral myocarditis; (10) patients with incomplete medical history records; (11) those with incomplete laboratory tests; and (12) those who refused treatment during hospitalization.…”

Section: Methodsmentioning

confidence: 99%

“…10,11 Alterations in the expression levels of specific lncRNAs have been observed in animal models of sepsis and manipulating their expression can impact myocardial cell damage. 12,13 Despite substantial progress in unraveling the pathogenesis of sepsis, the precise mechanism by which lncRNAs regulate myocardial cell injury remains elusive. 14 Moreover, although B-type natriuretic peptide (BNP), creatine kinase-MB, and cardiac troponin I (cTnI) are recognized markers of myocardial damage, their detection occurs after injury with a significant time delay.…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel lncRNA in Diagnosis of Sepsis-Induced Cardiomyopathy Using a Comprehensive Analysis of lncRNA-mRNA Network

Li,

Liu,

Tang

et al. 2023

J Pediatr Infect Dis

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Objective Long noncoding RNAs (lncRNAs) have been implicated in various biological processes, particularly in the regulation of inflammatory responses and myocardial injuries. Notably, the role of lncRNAs in sepsis-induced cardiomyopathy (SIC) has been highlighted. However, a comprehensive analysis investigating the specific circulating lncRNAs associated with SIC has yet to be conducted. Therefore, we conducted a study involving samples from healthy controls, sepsis patients without myocardial injuries, individuals with cardiac dysfunction following heart surgery, and those with SIC, aiming to identify the distinct lncRNAs involved in SIC. Methods A total of 12 blood samples were collected, including healthy controls, sepsis patients without myocardial injuries, patients with cardiac surgery-related myocardial injuries, and patients with SIC, who were aged from 10 to 22 months. Transcriptome sequencing was conducted to identify differentially expressed (DE) lncRNAs and mRNAs. Venn plots were employed to identify the DE RNAs specific to SIC. Subsequently, enrichment analyses were performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms. A coexpression network between lncRNAs and mRNAs was constructed, focusing on protein–protein interaction features. Then, further validation had been done in a consecutive larger cohort. Results We identified independent DE mRNAs and lncRNAs specific to SIC patients. The analysis of DE mRNAs revealed that immune activation, particularly innate immune activity, was the primary distinction between sepsis with or without myocardial injuries. Furthermore, cytokine production, particularly interleukin-1 secretion, played a significant role in inducing SIC. The expression profiles of DE lncRNAs showed considerable enrichment in shared topics with mRNAs. Subsequently, we identified lncRNAs targeting the DE mRNAs, many of which were involved in immune responses and cytokine production. We established a coexpression network between lncRNAs and mRNAs, leading to the discovery of a novel lncRNA (TCONS_00136255). Finally, we successfully validated TCONS_00136255, demonstrating its acceptable diagnostic accuracy and its role in regulating major molecular processes involved in SIC. Conclusion lncRNAs actively participate in the significant biological changes associated with immune responses in sepsis-induced myocardial injuries. These lncRNAs interact with mRNAs to modulate inflammation activity and cytokine production. Notably, the identification of the novel lncRNA (TCONS_00136255) highlights its crucial regulatory role in SIC.

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Molecular Mechanism of Sevoflurane Preconditioning Based on Whole-transcriptome Sequencing of Lipopolysaccharide-induced Cardiac Dysfunction in Mice

Cited by 6 publications

References 52 publications

Identification of TGF-β-related genes in cardiac hypertrophy and heart failure based on single cell RNA sequencing

Identification of TGF-β-related genes in cardiac hypertrophy and heart failure based on single cell RNA sequencing

Integration of transcriptomic, proteomic, and metabolomic data to identify lncRNA rPvt1 associations in lipopolysaccharide-treated H9C2 cardiomyocytes

Identification of a Novel lncRNA in Diagnosis of Sepsis-Induced Cardiomyopathy Using a Comprehensive Analysis of lncRNA-mRNA Network

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