The Roles of Cardiac Fibroblasts and Endothelial Cells in Myocarditis

Xuan, Yunling; Chen, Chen; Wen, Zheng; Wang, Dao Wen

doi:10.3389/fcvm.2022.882027

Cited by 11 publications

(8 citation statements)

References 101 publications

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“…Given stromal cells such as endothelial cells, pericytes, and fibroblasts play crucial roles in orchestrating cardiac immune responses 61,62 , we next investigated the contribution of the non-immune cell component captured in our heart data to irMyocarditis. Subclustering of scRNA-seq data from 65,409 cells yielded 17 distinct non-immune subsets (excluding doublets and RBCs): eight endothelial populations, three pericyte populations, fibroblasts, myofibroblasts, smooth muscle cells, endocardial cells, neuronal cells, and cardiomyocytes ( Figure 5a-b, Supplementary Figure 7a-b, Supplementary Table 9, Methods ).…”

Section: Resultsmentioning

confidence: 99%

Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor

Blum,

Zlotoff,

Smith

et al. 2023

Preprint

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Immune checkpoint inhibitors (ICIs) are widely used anti-cancer therapies that can cause morbid and potentially fatal immune-related adverse events (irAEs). ICI-related myocarditis (irMyocarditis) is uncommon but has the highest mortality of any irAE. The pathogenesis of irMyocarditis and its relationship to anti-tumor immunity remain poorly understood. We sought to define immune responses in heart, tumor, and blood during irMyocarditis and identify biomarkers of clinical severity by leveraging single-cell (sc)RNA-seq coupled with T cell receptor (TCR) sequencing, microscopy, and proteomics analysis of 28 irMyocarditis patients and 23 controls. Our analysis of 284,360 cells from heart and blood specimens identified cytotoxic T cells, inflammatory macrophages, conventional dendritic cells (cDCs), and fibroblasts enriched in irMyocarditis heart tissue. Additionally, potentially targetable, pro-inflammatory transcriptional programs were upregulated across multiple cell types. TCR clones enriched in heart and paired tumor tissue were largely non-overlapping, suggesting distinct T cell responses within these tissues. We also identify the presence of cardiac-expanded TCRs in a circulating, cycling CD8 T cell population as a novel peripheral biomarker of fatality. Collectively, these findings highlight critical biology driving irMyocarditis and putative biomarkers for therapeutic intervention.

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Section: Resultsmentioning

confidence: 99%

Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor

Blum,

Zlotoff,

Smith

et al. 2023

Preprint

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“…1 ). For instance, they can further stimulate cytokine release from cardiomyocytes [ 123 ], endothelial cells [ 124 ], and cardiac fibroblasts [ 125 ]. Of particular interest is the multifunctional cytokine transforming growth factor-β1 (TGF-β1), found elevated in plasma from FD patients and associated with fibrotic progression and cardiac remodeling [ 126 ].…”

Section: Inflammation In Fabry Diseasementioning

confidence: 99%

Fabry Disease: Cardiac Implications and Molecular Mechanisms

Weissman,

Dudek,

Sequeira

et al. 2024

Curr Heart Fail Rep

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Purpose of Review This review explores the interplay among metabolic dysfunction, oxidative stress, inflammation, and fibrosis in Fabry disease, focusing on their potential implications for cardiac involvement. We aim to discuss the biochemical processes that operate in parallel to sphingolipid accumulation and contribute to disease pathogenesis, emphasizing the importance of a comprehensive understanding of these processes. Recent Findings Beyond sphingolipid accumulation, emerging studies have revealed that mitochondrial dysfunction, oxidative stress, and chronic inflammation could be significant contributors to Fabry disease and cardiac involvement. These factors promote cardiac remodeling and fibrosis and may predispose Fabry patients to conduction disturbances, ventricular arrhythmias, and heart failure. While current treatments, such as enzyme replacement therapy and pharmacological chaperones, address disease progression and symptoms, their effectiveness is limited. Summary Our review uncovers the potential relationships among metabolic disturbances, oxidative stress, inflammation, and fibrosis in Fabry disease–related cardiac complications. Current findings suggest that beyond sphingolipid accumulation, other mechanisms may significantly contribute to disease pathogenesis. This prompts the exploration of innovative therapeutic strategies and underscores the importance of a holistic approach to understanding and managing Fabry disease.

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“…This assumption was confirmed via the transfection of ADSC-derived exosomes into MI-induced mice and observing a decrease in cardiac fibrosis, an increase in angiogenesis, and an improvement of cardiac function [ 77 ]. Cardiac fibroblast-derived EVs modulate cardiac remodeling, favoring intercellular communication between cardiomyocytes (CM) and cardiac fibroblasts [ 78 , 79 ]. Consistently, exosomal miRNA-21 CM-derived, reduced the expression of sarcoplasmic protein sorbin 2 containing SH3 domain (SORBS2) and PDZ and LIM domain 5 (PDLIM5), producing an increase in cell size and stimulating cardiomyocyte hypertrophy [ 80 , 81 ].…”

Section: The Epigenetic Role Of Evs In Cardiovascular Damagementioning

confidence: 99%

Basic Pathogenic Mechanisms and Epigenetic Players Promoted by Extracellular Vesicles in Vascular Damage

Schiano

Balbi²,

Nigris

et al. 2023

IJMS

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Both progression from the early pathogenic events to clinically manifest cardiovascular diseases (CVD) and cancer impact the integrity of the vascular system. Pathological vascular modifications are affected by interplay between endothelial cells and their microenvironment. Soluble factors, extracellular matrix molecules and extracellular vesicles (EVs) are emerging determinants of this network that trigger specific signals in target cells. EVs have gained attention as package of molecules with epigenetic reversible activity causing functional vascular changes, but their mechanisms are not well understood. Valuable insights have been provided by recent clinical studies, including the investigation of EVs as potential biomarkers of these diseases. In this paper, we review the role and the mechanism of exosomal epigenetic molecules during the vascular remodeling in coronary heart disease as well as in cancer-associated neoangiogenesis.

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The Roles of Cardiac Fibroblasts and Endothelial Cells in Myocarditis

Cited by 11 publications

References 101 publications

Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor

Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor

Fabry Disease: Cardiac Implications and Molecular Mechanisms

Basic Pathogenic Mechanisms and Epigenetic Players Promoted by Extracellular Vesicles in Vascular Damage

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