Perez-Shibayama, Christian; Gil-Cruz, Cristina; Cadosch, Nadine; Lütge, Mechthild; Cheng, Hung-Wei; De Martin, Angelina; Frischmann, Kira; Joachimbauer, Anna; Onder, Lucas; Papadopoulou, Iliana; Papadopoulou, Chrysa; Ring, Sandra; Krebs, Philippe; Vu, Vivian P.; Nägele, Matthias P.; Rossi, Valentina A.; Parianos, Danaë; Zsilavecz, Valentin W.; Cooper, Leslie T.; Flammer, Andreas; ... (2024). Bone morphogenic protein-4 availability in the cardiac microenvironment controls inflammation and fibrosis in autoimmune myocarditis. Nature cardiovascular research Springer Nature 10.1038/s44161-024-00432-0
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Myocarditis is an inflammatory heart disease that leads to loss of cardiomyocytes and frequently precipitates fibrotic remodeling of the myocardium, culminating in heart failure. However, the molecular mechanisms underlying immune cell control and maintenance of tissue integrity in the inflamed cardiac microenvironment remain elusive. In this study, we found that bone morphogenic protein-4 (BMP4) gradients maintain cardiac tissue homeostasis by single-cell transcriptomics analyses of inflamed murine and human myocardial tissues. Cardiac BMP pathway dysregulation was reflected by reduced BMP4 serum concentration in patients with myocarditis. Restoration of BMP signaling by antibody-mediated neutralization of the BMP inhibitors gremlin-1 and gremlin-2 ameliorated T cell-induced myocardial inflammation in mice. Moreover, progression to inflammatory cardiomyopathy was blocked through the reduction of fibrotic remodeling and preservation of cardiomyocyte integrity. These results unveil the BMP4–gremlin axis as a druggable pathway for the treatment of myocardial inflammation, limiting the severe sequelae of cardiac fibrosis and heart failure.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology 04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Krebs, Philippe, Vu, Vivian Pham |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2731-0590 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Philippe Krebs |
Date Deposited: |
26 Feb 2024 10:42 |
Last Modified: |
26 Feb 2024 10:42 |
Publisher DOI: |
10.1038/s44161-024-00432-0 |
BORIS DOI: |
10.48350/193258 |
URI: |
https://boris.unibe.ch/id/eprint/193258 |
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