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Bone morphogenic protein-4 availability in the cardiac microenvironment controls myocardial inflammation and fibrosis - Single cell transcriptome analysis from healthy and inflamed murine hearts

ABSTRACT: Myocarditis is a heart condition that causes inflammation and results in the loss of heart muscle cells, often leading to fibrosis (scarring) of the heart tissue and heart failure. However, the molecular mechanisms underlying immune cell control and maintenance of tissue integrity in the inflamed cardiac microenvironment remain elusive. Based on our finding that bone morphogenic protein-4 (BMP4) serum concentration was reduced in myocarditis patients in combination with comprehensive single cell and single nucleus RNA sequencing analyses of inflamed murine and human myocardial tissue indicated that BMP4 gradients maintain cardiac tissue homeostasis. Indeed, restoration of BMP signaling through antibody-mediated neutralization of the BMP-inhibitors GREM1 and GREM2 reduced CD4+ T cell-mediated myocardial inflammation and blocked disease progression by reduction of adverse fibrotic remodelling. These results unveil a key function of the BMP4-GREM1/2 axis as promising approach for treating myocardial inflammation and the serious complications of cardiac fibrosis and heart failure.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Mechthild Lütge

PROVIDER: E-MTAB-12589 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Bone morphogenic protein-4 availability in the cardiac microenvironment controls myocardial inflammation and fibrosis - Single nucleus RNA sequencing data from healthy and inflamed murine hearts

Project description:Myocarditis is a heart condition that causes inflammation and results in the loss of heart muscle cells, often leading to fibrosis (scarring) of the heart tissue and heart failure. However, the molecular mechanisms underlying immune cell control and maintenance of tissue integrity in the inflamed cardiac microenvironment remain elusive. Based on our finding that bone morphogenic protein-4 (BMP4) serum concentration was reduced in myocarditis patients in combination with comprehensive single cell and single nucleus RNA sequencing analyses of inflamed murine and human myocardial tissue indicated that BMP4 gradients maintain cardiac tissue homeostasis. Indeed, restoration of BMP signaling through antibody-mediated neutralization of the BMP-inhibitors GREM1 and GREM2 reduced CD4+ T cell-mediated myocardial inflammation and blocked disease progression by reduction of adverse fibrotic remodelling. These results unveil a key function of the BMP4-GREM1/2 axis as promising approach for treating myocardial inflammation and the serious complications of cardiac fibrosis and heart failure.

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Titered FOXO overexpression maintains cardiac proteostasis and ameliorates age-associated functional decline

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Hormonal Therapies Upregulate MANF and Overcome Female Susceptibility to Immune Checkpoint Inhibitor-Myocarditis

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