Platelet SR-PSOX/CXCL16–CXCR6 Axis Influences Thrombotic Propensity and Prognosis in Coronary Artery Disease

Guan, Tianyun; Emschermann, Fréderic; Schories, Christoph; Groga‐Bada, Patrick; Martus, Peter; Gawaz, Meinrad; Geisler, Tobias; Rath, Dominik; Chatterjee, Mainak

doi:10.3390/ijms231911066

Cited by 6 publications

(1 citation statement)

References 35 publications

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“… 33 , 34 Th1 cells can produce a high level of interferon-γ and promote arteriosclerosis by local effects on the arterial wall that affect lipid metabolism. 35 , 36 Th2 cells can antagonize atherosclerosis by secreting interleukin (IL)-4 and IL-10. 37 , 38 The proportions of Th17 and its secreted IL-17 in CAD and atherosclerosis are increased, and positively correlated with the severity of the disease.…”

Section: Discussionmentioning

confidence: 99%

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

He,

Muhetaer,

et al. 2023

JIR

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Background: Coronary artery disease (CAD) is a multifactorial immune disease, but research into the specific immune mechanism is still needed. The present study aimed to identify novel immune-related markers of CAD. Methods: Three CAD-related datasets (GSE12288, GSE98583, GSE113079) were downloaded from the Gene Expression Integrated Database. Gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and weighted gene coexpression network analysis were performed on the common significantly differentially expressed genes (DEGs) of these three data sets, and the most relevant module genes for CAD obtained. The immune cell infiltration of module genes was evaluated with the CIBERSORT algorithm, and characteristic genes accompanied by their diagnostic effectiveness were screened by the machine-learning algorithm least absolute shrinkage and selection operator (LASSO) regression analysis. The expression levels of characteristic genes were evaluated in the peripheral blood mononuclear cells of CAD patients and healthy controls for verification. Results: A total of 204 upregulated and 339 downregulated DEGs were identified, which were mainly enriched in the following pathways: "Apoptosis", "Th17 cell differentiation", "Th1 and Th2 cell differentiation", "Glycerolipid metabolism", and "Fat digestion and absorption". Five characteristic genes, LMAN1L, DOK4, CHFR, CEL and CCDC28A, were identified by LASSO analysis, and the results of the immune cell infiltration analysis indicated that the proportion of immune infiltrating cells (activated CD8 T cells and CD56 DIM natural killer cells) in the CAD group was lower than that in the control group. The expressions of CHFR, CEL and CCDC28A in the peripheral blood of the healthy controls and CAD patients were significantly different. Conclusion:We identified CHFR, CEL and CCDC28A as potential biomarkers related to immune infiltration in CAD based on public data sets and clinical samples. This finding will contribute to providing a potential target for early noninvasive diagnosis and immunotherapy of CAD.

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Section: Discussionmentioning

confidence: 99%

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

He,

Muhetaer,

et al. 2023

JIR

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Screening of the Key Genes and Signaling Pathways for Schizophrenia Using Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad,

Vastrad

2023

Preprint

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Schizophrenia is thought to be the most prevalent chronic psychiatric disorder. Numerous proteins have been identified that are associated with the occurrence and development of schizophrenia. This study aimed to identify potential core genes and pathways involved in schizophrenia, through exhaustive bioinformatic and next generation sequencing (NGS) data analyses using GSE20966 NGS data of neural progenitor cells and neurons obtained from healthy controls and patients with schizophrenia. The NGS data were downloaded from the Gene Expression Omnibus database. NGS data was processed by the DESeq2 package in R software and the differentially expressed genes (DEGs) were identified. Gene Ontology (GO) enrichment analysis and REACTOME pathway enrichment analysis were carried out to identify potential biological functions and pathways of the DEGs. Protein-protein interaction (PPI) network, module, miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were performed to identify the hub genes, miRNA and TFs. Potential hub genes were analyzed using receiver operating characteristic (ROC) curves in the R package (pROC). In this investigation, an overall 955 DEGs were identified: 478 genes were remarkably up regulated and 477 genes were distinctly down regulated. These genes were enriched for GO terms and pathways mainly involved in the multicellular organismal process, GPCR ligand binding, regulation of cellular process and amine ligand-binding receptors. MYC, FN1, CDKN2A, EEF1G, CAV1, ONECUT1, SYK, MAPK13, TFAP2A and BTK were considered the potential hub genes. miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed successfully. On the whole, the findings of this investigation enhance our understanding of the potential molecular mechanisms of schizophrenia and provide potential targets for further investigation.

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Chemokines, molecular drivers of thromboinflammation and immunothrombosis

Leberzammer,

von Hundelshausen

2023

Front. Immunol.

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Blood clotting is a finely regulated process that is essential for hemostasis. However, when dysregulated or spontaneous, it promotes thrombotic disorders. The fact that these are triggered, accompanied and amplified by inflammation is reflected in the term thromboinflammation that includes chemokines. The role of chemokines in thrombosis is therefore illuminated from a cellular perspective, where endothelial cells, platelets, red blood cells, and leukocytes may be both the source and target of chemokines. Chemokine-dependent prothrombotic processes may thereby occur independently of chemokine receptors or be mediated by chemokine receptors, although the binding and activation of classical G protein-coupled receptors and their signaling pathways differ from those of atypical chemokine receptors, which do not function via cell activation and recruitment. Regardless of binding to their receptors, chemokines can induce thrombosis by forming platelet-activating immune complexes with heparin or other polyanions that are pathognomonic for HIT and VITT. In addition, chemokines can bind to NETs and alter their structure. They also change the electrical charge of the cell surface of platelets and interact with coagulation factors, thereby modulating the balance of fibrinolysis and coagulation. Moreover, CXCL12 activates CXCR4 on platelets independently of classical migratory chemokine activity and causes aggregation and thrombosis via the PI3Kβ and Btk signaling pathways. In contrast, typical chemokine-chemokine receptor interactions are involved in the processes that contribute to the adhesiveness of the endothelium in the initial phase of venous thrombosis, where neutrophils and monocytes subsequently accumulate in massive numbers. Later, the reorganization and resolution of a thrombus require coordinated cell migration and invasion of the thrombus, and, as such, indeed, chemokines recruit leukocytes to existing thrombi. Therefore, chemokines contribute in many independent ways to thrombosis.

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Platelet SR-PSOX/CXCL16–CXCR6 Axis Influences Thrombotic Propensity and Prognosis in Coronary Artery Disease

Cited by 6 publications

References 35 publications

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

Immune Cell Infiltration Analysis Based on Bioinformatics Reveals Novel Biomarkers of Coronary Artery Disease

Screening of the Key Genes and Signaling Pathways for Schizophrenia Using Bioinformatics and Next Generation Sequencing Data Analysis

Chemokines, molecular drivers of thromboinflammation and immunothrombosis

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