Analysis of susceptibility genes and myocardial infarction risk correlation of ischemic cardiomyopathy based on bioinformatics

Nai, Zhang; Yang, Chen; Liu, Yujuan; Zeng, Peng; Gong, Tao; Lü, Tao; Li, Xin-Ai

doi:10.21037/jtd-22-1060

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…Raw expression data of datasets GSE160516 and GSE61592 were downloaded from the GEO database, and the “limma package” of R software (version 4.0.1) was used to screen differentially expressed genes (DEGs) between reperfusion (myocardial tissue with a reperfusion time of 72 h) and sham myocardium [ 21 ]. The p -value was corrected by the Benjamini–Hochberg method.…”

Section: Methodsmentioning

confidence: 99%

Expression Pattern and Molecular Mechanism of Oxidative Stress-Related Genes in Myocardial Ischemia–Reperfusion Injury

Luo

Cai

et al. 2023

JCDD

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(1) Background: The molecular mechanism of oxidative stress-related genes (OSRGs) in myocardial ischemia–reperfusion injury (MIRI) has not been fully elucidated. (2) Methods: Differential expression analysis, enrichment analysis, and PPI analysis were performed on the MIRI-related datasets GSE160516 and GSE61592 to find key pathways and hub genes. OSRGs were obtained from the Molecular Signatures Database (MSigDB). The expression pattern and time changes of them were studied on the basis of their raw expression data. Corresponding online databases were used to predict miRNAs, transcription factors (TFs), and therapeutic drugs targeting common differentially expressed OSRGs. These identified OSRGs were further verified in the external dataset GSE4105 and H9C2 cell hypoxia–reoxygenation (HR) model. (3) Results: A total of 134 DEGs of MIRI were identified which were enriched in the pathways of “immune response”, “inflammatory response”, “neutrophil chemotaxis”, “phagosome”, and “platelet activation”. Six hub genes and 12 common differentially expressed OSRGs were identified. A total of 168 miRNAs, 41 TFs, and 21 therapeutic drugs were predicted targeting these OSRGs. Lastly, the expression trends of Aif1, Apoe, Arg1, Col1a1, Gpx7, and Hmox1 were confirmed in the external dataset and HR model. (4) Conclusions: Aif1, Apoe, Arg1, Col1a1, Gpx7, and Hmox1 may be involved in the oxidative stress mechanism of MIRI, and the intervention of these genes may be a potential therapeutic strategy.

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Section: Methodsmentioning

confidence: 99%

Expression Pattern and Molecular Mechanism of Oxidative Stress-Related Genes in Myocardial Ischemia–Reperfusion Injury

Luo

Cai

et al. 2023

JCDD

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“…Experience has shown that bioinformatics technology has great application value in the screening of disease biomarkers, which is of great significance for the diagnosis, treatment, and prognosis of diseases, and can provide a more comprehensive and profound understanding of diseases ( 11 - 14 ). A recent study showed that differentially expressed genes (DEGs) were significantly enriched in metabolic pathways, oxidative phosphorylation, and extracellular matrix (ECM) receptor interactions, and were closely related to fibrosis, collagen catabolic process and inflammatory response function ( 15 ). Interleukin-6 ( IL-6 ) and Ras homologous gene family member A ( RHOA ) may play an important role in the development of ICM, IL-6 and RHOA , however, the value of the IL-6 and RHOA in ICM was poorly studied, further studies are needed to identify new biomarkers in myocardial ischemia.…”

Section: Introductionmentioning

confidence: 99%

Screening and identification of hub genes for ischemic cardiomyopathy and construction and validation of a clinical prognosis model using bioinformatics analysis

Wang,

Tang,

Bai

et al. 2024

J Thorac Dis

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Background Myocardial ischemia and hypoxia may result in myocardial cell necrosis, scar formation, and hyperplasia. We aim to explore the differentially expressed genes (DEGs) in ischemic cardiomyopathy (ICM), construct and identify a clinical prognosis model using bioinformatics methods, so as to screen potential biomarkers of ICM to provide a basis for the early diagnosis and treatment of ICM. Methods Based on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, R language was used to screen DEGs in healthy myocardial (n=5) and ICM myocardial tissues (n=12). DEGs were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI). Receiver operating characteristic (ROC) curves were drawn to verify the target genes. Results A total of 259 genes with significantly changed fold change (FC) values were obtained through conditional screening, including up-regulated genes and down-regulated genes. The first two hub genes [interleukin-6 ( IL-6 ) and Ras homologous gene family member A ( RHOA )] with the largest degree value among the above up-regulated and down-regulated genes were selected and their expression values were combined in the gene chip to draw the ROC curve based on the pROC package of R language. The area under the ROC curve (AUC) values of IL-6 and RHOA were 0.956 and 0.995, respectively. The expression levels of Sqstm1, Nos2, IL-6, RHOA , and Zfp36 genes in the ICM group are lower than those in the blank control group and the difference was statistically significant (P<0.05). RHOA and Stat3 were identified as the key genes controlling the occurrence and development of ICM. Conclusions ICM is closely related to the changes of extracellular matrix (ECM) and oxidoreductase activity. The IL-6 and RHOA are expected to become potential targets for ICM treatment.

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“…Ischemic heart disease (IHD) is the leading contributor to the global burden of cardiovascular disease, which is primarily caused by coronary heart disease (CHD) ( 1 , 2 ). In IHD, coronary artery stenosis or occlusion leads to reduced myocardial blood perfusion, resulting in a series of clinical ischemic symptoms ( 3 ). With advancing age, the prevalence of IHD significantly increases, as it is an aging-related disease ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Association between regulatory T cells and ischemic heart disease: a Mendelian randomization study

Hou,

Si,

Yang

et al. 2024

J Thorac Dis

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Background An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy for exposure and can be used to inferentially determine the causal effect of exposure on outcomes. We thus used MR analysis to investigate whether there is a causal relationship between the biomarkers of Tregs and IHD. Methods Selected genetic variants (P<5.00E−08) from the summary data of a genome-wide association study (GWAS) were used to conduct a two-sample bidirectional MR analysis. The analysis included 51 extensive Treg subtypes involving 3,757 individuals from the general population. Summary statistics of IHD were obtained from the IEU open GWAS project, which contains 30,952 cases and 187,845 controls. The populations in both GWAS studies were of European ancestry. Results We identified a set of 197 single-nucleotide polymorphisms (SNPs) that served as instrumental variables (IVs) for evaluating 51 Treg subtypes. Thirteen significant variables were found to be potentially associated with IHD. After false-discovery rate (FDR) adjustment, we identified four Treg subtypes to be causally protective for IHD risk: CD28 on activated & secreting CD4 Tregs [odds ratio (OR) =0.89; 95% confidence interval (CI): 0.82–0.96; P=3.10E−03; adjusted P=0.04], CD28 on activated CD4 Tregs (OR =0.87; 95% CI: 0.80–0.95; P=3.10E−03; adjusted P=0.04), CD28 on CD4 Tregs (OR =0.87; 95% CI: 0.80–0.96; P=3.41E−03; adjusted P=0.04), and CD28 on resting CD4 Treg cell (OR =0.91; 95% CI: 0.85–0.97; P=3.48E−03; adjusted P=0.04). Reverse MR analysis found eight potential causal variables, but these associations were nonsignificant after FDR correction (all adjusted P values >0.05). Conclusions This study identified the significance of elevated CD28 expression on CD4 Tregs as a novel molecular modifier that may influence IHD occurrence, suggesting that targeting CD28 expression on CD4 Tregs could offer a promising therapeutic approach for IHD.

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Analysis of susceptibility genes and myocardial infarction risk correlation of ischemic cardiomyopathy based on bioinformatics

Cited by 3 publications

References 38 publications

Expression Pattern and Molecular Mechanism of Oxidative Stress-Related Genes in Myocardial Ischemia–Reperfusion Injury

Expression Pattern and Molecular Mechanism of Oxidative Stress-Related Genes in Myocardial Ischemia–Reperfusion Injury

Screening and identification of hub genes for ischemic cardiomyopathy and construction and validation of a clinical prognosis model using bioinformatics analysis

Association between regulatory T cells and ischemic heart disease: a Mendelian randomization study

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