The Role of B Cells in Cardiomyopathy and Heart Failure

Bermea, Kevin C.; Bhalodia, Aashik; Huff, Angelo; Rousseau, Sylvie; Adamo, Luigi

doi:10.1007/s11886-022-01722-4

Cited by 20 publications

(18 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely to ARVC, our results indicate that B cell interactions are greatly increased in DCM relative to controls. This is consistent with findings that B cell numbers are also increased in the peripheral blood of DCM patients 52 and with other clinical observations that suggest a pathogenic role of B cells in DCM 53 . Most notably, we found that in DCM B cells had considerably greater and stronger interactions with fibroblasts, epicardial fat cells, eosinophils, and stromal cells compared to controls (Figure 2F).…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Myocardial B cells have specific gene expression and predicted interactions in Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy

Bermea,

Duque,

Cohen

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background: A growing body of evidence from animal models indicates that the myocardium hosts a population of B cells that play a role in the development of cardiomyopathy. However, there is minimal data on human myocardial B cells and their biological niche within the heart remains mostly unexplored. Methods: We integrated single-cell and single-nuclei datasets from 45 healthy human hearts, 70 hearts with dilated cardiomyopathy (DCM), and 8 hearts with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Interactions between B cells and other cell types were investigated using the CellChat Package. Differential gene expression analysis comparing B cells across conditions was performed using DESeq2. Pathway analysis was performed using Ingenuity, KEGG, and GO pathways analysis. Results: Out of 1,200,752 nuclei and 49,723 cells, we identified 1,100 B cells, including naive B cells and plasma cells. B cells showed an extensive network of interactions within the healthy myocardium that included outgoing signaling to macrophages, T cells, endothelial cells, and pericytes, and incoming signaling from endothelial cells, pericytes, and fibroblasts. This biological niche relied on both ECM-receptor interactions, cell-cell contact interactions, and paracrine interaction, it changed significantly in the context of cardiomyopathy and had disease-specific features. Differential gene expression analysis showed that in the context of DCM both naive and plasma myocardial B cells upregulated several pathways related to immune activation, including upregulation of oxidative phosphorylation, upregulation of leukocyte extravasation and, in naive B cells, antigen processing and presentation. Conclusions: The human healthy and diseased myocardium contains naive B cells and plasma cells, integrated in a diverse and dynamic biological niche. Naive myocardial-associated B cells likely contribute to the pathogenesis of human dilated cardiomyopathy.

show abstract

Section: Discussionsupporting

confidence: 93%

“…(T32-HL007227). The content of this manuscript has been published online as a preprint in BioxRiv (76).…”

Section: Acknowledgmentsmentioning

confidence: 99%

Myocardial B cells have specific gene expression and predicted interactions in Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy

Bermea,

Duque,

Cohen

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Evidence suggests that B cells play a crucial role in HF with reduced ejection fraction via antibody and cytokine secretion. [40] The recruitment of B cells is significantly high from day 1 and remains high even after 14 days post-myocardial infraction. [41] B cell activation may further enhance the activation of the immune system and adverse cardiac changes, including fibrosis, hypertrophy, and contractile dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Identifying immune cell infiltration and diagnostic biomarkers in heart failure and osteoarthritis by bioinformatics analysis

Wen¹,

Liu

Qin

et al. 2023

Medicine

View full text Add to dashboard Cite

Heart failure (HF) and osteoarthritis (OA) are medical conditions that can significantly impact daily activities. Evidence has shown that HF and OA may share some pathogenic mechanisms. However, the underlying genomic mechanisms remain unclear. This study aimed to explore the underlying molecular mechanism and identify diagnostic biomarkers for HF and OA. With the cutoff criteria of fold change (FC) > 1.3 and P < .05, 920, 1500, 2195, and 2164 differentially expressed genes (DEGs) were identified in GSE57338, GSE116250, GSE114007, and GSE169077, respectively. After making the intersection of DEGs, we obtained 90 upregulated DEGs and 51 downregulated DEGs in HF datasets and 115 upregulated DEGs and 75 downregulated DEGs in OA datasets. Afterward, we conducted genome ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, protein-protein interaction (PPI) networks, and hub genes screening based on DEGs. Then, 4 common DEGs (fibroblast activation protein alpha [FAP], secreted frizzled-related protein 4 (SFRP4), Thy-1 cell surface antigen (THY1), matrix remodeling associated 5 [MXRA5]) between HF and OA were screened and validated in GSE5406 and GSE113825 datasets, based on which we established the support vector machine (SVM) models. The combined area under the receiver operating characteristic curve (AUC) of THY1, FAP, SFRP4, and MXRA5 in the HF training and test sets reached 0.949 and 0.928. While in the OA training set and test set, the combined AUC of THY1, FAP, SFRP4, and MXRA5 reached 1 and 1, respectively. The analysis of immune cells in HF revealed high levels of dendritic cell (DC), B cells, natural killer T cell (NKT), Type 1 regulatory T cell (Tr1), cytotoxic T cell (Tc), exhausted T cell (Tex), and mucosal-associated invariant T cell (MAIT), while displaying lower levels of monocytes, macrophages, NK, CD4 + T, gamma delta T (γδ T), T helper type 1 (Th1), T helper type 2 (Th2), and effector memory T cell (Tem). Moreover, the 4 common DEGs were positively correlated with DCs and B cells and negatively correlated with γδ T. In OA patients, the abundance of monocyte, macrophage, CD4 + naïve, and natural T regulatory cell (nTreg) was higher, while the infiltration of CD8 + T, γδ T, CD8 + naïve, and MAIT was lower. The expression of THY1 and FAP was significantly correlated with macrophage, CD8 + T, nTreg, and CD8 + naïve. SFRP4 was correlated with monocyte, CD8 + T, γδ T, CD4 + naïve, nTreg, CD8 + naïve and MAIT. MXRA5 was correlated with macrophage, CD8 + T, nTreg and CD8 + naïve. FAP, THY1, MXRA5, and SFRP4 may be diagnostic biomarkers for both HF and OA, and their correlation with immune cell infiltrations suggests shared immune pathogenesis.

show abstract

“…In summary, we describe the first reproducible, optimized, clinically relevant murine model of T . brucei-associated cardiac disease, a feature of African trypanosomiasis that is often overlooked in current textbooks and clinical resources 53,54 . In the context of this model’s characterization, we produced evidence suggesting that T. brucei -associated cardiac damage is an immune-mediated event.…”

Section: Discussionmentioning

confidence: 99%

A murine model ofTrypanosoma brucei-induced myocarditis and cardiac dysfunction

Crilly,

Zita,

Beaver

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Trypanosoma brucei is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of T. brucei infection. However, despite the importance of T. brucei as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of T. brucei-associated cardiomyopathy. We present the first clinically relevant, reproducible murine model of cardiac dysfunction in chronic T. brucei infection. Similar to humans, mice showed histological evidence of myocarditis and elevation of serum NT-proBNP. Serum NT-proBNP levels were elevated prior to the development of severe ventricular dysfunction. On flow cytometry, myocarditis was associated with an increase of most myocardial immune cell populations, including multiple T cell and macrophage subsets, corroborating the notion that T. brucei-associated cardiac damage is an immune-mediated event. This novel mouse model represents a powerful and practical tool to investigate the pathogenesis of T. brucei-mediated heart damage and support the development of therapeutic options for T. brucei-associated cardiac disease.

show abstract

The Role of B Cells in Cardiomyopathy and Heart Failure

Cited by 20 publications

References 108 publications

Myocardial B cells have specific gene expression and predicted interactions in Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy

Myocardial B cells have specific gene expression and predicted interactions in Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy

Identifying immune cell infiltration and diagnostic biomarkers in heart failure and osteoarthritis by bioinformatics analysis

A murine model ofTrypanosoma brucei-induced myocarditis and cardiac dysfunction

Contact Info

Product

Resources

About