Immune cell infiltration landscapes in pediatric acute myocarditis analyzed by CIBERSORT

Kawada, Junji; Takeuchi, Suguru; Imai, Hiroshi; Okumura, Toshihiko; Horiba, Kazuhiro; Suzuki, Takehiko; Torii, Yuka; Yasuda, Kazushi; Imanaka‐Yoshida, Kyoko; Ito, Yoshinori

doi:10.1016/j.jjcc.2020.08.004

Cited by 94 publications

(83 citation statements)

References 23 publications

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“…Badve et al reported integration of mutations with CIBERSORT analysis could provide better prediction of outcomes and novel therapeutic targets in Triple Negative Breast Cancer (23). Kawada et al indicated that Infiltrating immune cell subsets detected by CIBERSORT analysis can reflect the time course of innate and adaptive immune responses in acute myocarditis and suggested that CIBERSORT is a promising tool to analyze immune cell landscapes and provide novel insights into the pathogenesis of acute myocarditis (10).…”

Section: Discussionmentioning

confidence: 99%

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Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Gao

Sun

Liu

et al. 2021

Front. Cardiovasc. Med.

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Background: Stanford type A aortic dissection (AAD) is a catastrophic disease. An immune infiltrate has been found within the aortic wall of dissected aortic specimens. The recall and activation of macrophages are key events in the early phases of AAD. Herein, the immune filtration profile of AAD was uncovered.Methods: Gene expression data from the GSE52093, GSE98770 and GSE153434 datasets were downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) of each dataset were calculated and then integrated. A protein-protein interaction (PPI) network was established with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the hub genes were identified in Cytoscape. Furthermore, gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of hub genes were performed. Finally, we set GSE52093 and GSE98770 as the training set and GSE153434 as the validation set to assess immune infiltration in AAD using CIBERSORTx and analyzed the correlations between immune cells and hub genes in both the training and validation sets.Results: Sixty-one integrated DEGs were identified. The top 10 hub genes were selected from the PPI network, and 140 biological process (BP) terms and 12 pathways were enriched among the top 10 hub genes. The proportions of monocytes and macrophages were significantly higher in AAD tissues than in normal tissues. Notably, this result was consistent in the training set and the validation set. In addition, we found that among the hub genes, CA9, CXCL5, GDF15, VEGFA, CCL20, HMOX1, and SPP1 were positively correlated with CD14, a cell marker of monocytes, while CA9, CXCL5, GDF15, and VEGFA were positively correlated with CD68, a cell marker of macrophages in the training set. Finally, according to the results of the GO and KEGG analysis of hub genes, we found that the monocyte/macrophage-related genes were involved in immune-inflammatory responses through degradation of the extracellular matrix, endothelial cell apoptosis, hypoxia and the interaction of cytokines and chemokines.Conclusion: The monocyte-macrophage system plays a major role in immune-inflammatory responses in the development of AAD. Several hub genes are involved in this process via diverse mechanisms.

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Section: Discussionmentioning

confidence: 99%

“…CIBERSORT, a bioinformatics tool, can distinguish and quantify 22 human immune cell types using a deconvolution algorithm based on gene expression data (8). Previous studies have shown that CIBERSORT can be used accurately to evaluate the composition of immune cells in many malignant tumors and non-malignant diseases (9,10).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Gao

Sun

Liu

et al. 2021

Front. Cardiovasc. Med.

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“…Myocarditis is an inflammatory condition in the myocardium that is histopathologically defined by inflammatory cell infiltration adjacent to cardiomyocytes and is classified as follows based on the predominant type of infiltrating cell: lymphocytic, eosinophilic, giant cell, or granulomatous [ 112 ].Lymphocytic myocarditis is the most common type and is characterized by the predominant infiltration of CD4- and CD8-positive T lymphocytes associated with CD68-positive macrophages [ 113 ]. However, the cell profile of infiltrates may vary according to the stage of disease [ 114 ].…”

Section: Myocarditismentioning

confidence: 99%

Tenascin-C in Heart Diseases—The Role of Inflammation

Imanaka‐Yoshida

2021

IJMS

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Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.

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“…This exposed a high degree of cardiomyocyte gene marker expression relative to other cell type markers, and no racial differences were seen. Due to the documented importance of immune cell composition on cardiac phenotype (18,56), in-silico method of cellular deconvolution was performed using CIBERSORT (36) to infer relative enrichment of immunologic cell-types in our cardiac samples (Supplemental Figure S6); again, no racial differences were noted. Therefore, gene expression analysis is unlikely confounded by cardiac tissue composition.…”

Section: Transcriptome-wide Cardiac Gene Expressionmentioning

confidence: 99%

Racial and socioeconomic disparity associates with differences in cardiac DNA methylation among men with end-stage heart failure

Pepin

Potter

et al. 2021

American Journal of Physiology-Heart and Circulatory Physiology

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Heart Failure (HF) is a multifactorial syndrome that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half of HF patients respond to guideline-directed medical management, prompting therapeutic efforts to confront the molecular underpinnings of its heterogeneity. In the current study, we examined epigenetics as a yet unexplored source of heterogeneity among patients with end-stage HF. Specifically, a multicohort-based study was designed to quantify cardiac genome-wide cytosine-p-guanine (CpG) methylation of cardiac biopsies from male patients undergoing left ventricular assist device (LVAD) implantation. In both pilot (n = 11) and testing (n = 31) cohorts, unsupervised multidimensional scaling of genome-wide myocardial DNA methylation exhibited a bimodal distribution of CpG methylation found largely to occur in the promoter regions of metabolic genes. Among the available patient attributes, only categorical self-identified patient race could delineate this methylation signature, with African American (AA) and Caucasian American (CA) samples clustering separately. Because race is a social construct, and thus a poor proxy of human physiology, extensive review of medical records was conducted, but ultimately failed to identify co-variates of race at the time of LVAD surgery. By contrast, retrospective analysis exposed a higher all-cause mortality among AA (56.3%) relative to CA (16.7%) patients at 2 years following LVAD placement (P=0.03). Geocoding-based approximation of patient demographics uncovered disparities in income levels among AA relative to CA patients. Therefore, although additional studies are needed, the current analysis implicates cardiac DNA methylation as a previously unrecognized indicator of socioeconomic disparity in human heart failure outcomes.

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Immune cell infiltration landscapes in pediatric acute myocarditis analyzed by CIBERSORT

Cited by 94 publications

References 23 publications

Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Analysis of Hub Genes and the Mechanism of Immune Infiltration in Stanford Type a Aortic Dissection

Tenascin-C in Heart Diseases—The Role of Inflammation

Racial and socioeconomic disparity associates with differences in cardiac DNA methylation among men with end-stage heart failure

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