Increase in mechanical load and pro-fibrotic stimulation leads to fibrotic and hypertrophic remodeling in porcine living myocardial slices

Heart failure (HF) is a growing global health concern, driven by factors such as increased mechanical load of the heart muscle tissue. This pathogenic condition is the result of remodeling processes, partially mediated by the cytokine transforming growth factor β (TGF- β1), with progressive depositi...

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Published in:Scientific reports Vol. 15; no. 1; pp. 41180 - 14
Main Authors: Bentele, Marco, Linke, Sophie, Neumüller, Susanne, Korte, Andrea, Gietz, Anika, Just, Annette, Stucki-Koch, Angelika, Pfanne, Angelika, Liu, Junqing, Zhao, Jiahao, Schwennen, Cornelia, Homann, Christian, Visscher, Christian, Pflaum, Michael, Wiegmann, Bettina, Bär, Christian, Weber, Natalie, Fiedler, Jan, Thum, Thomas
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 21.11.2025
Nature Publishing Group
Nature Portfolio
Subjects:
(up to 6): Cardiovascular diseases
631/443/592/1540
631/443/592/75
692/4019
Animals
Cardiac muscle
Cell culture
Collagen
Collagen - metabolism
Congestive heart failure
Disease Models, Animal
Extracellular matrix
Extracellular Matrix - metabolism
Fibroblast activation
Fibroblasts
Fibrosis
Global health
Heart failure
Heart Failure - metabolism
Heart Failure - pathology
Heart Failure - physiopathology
Heart Ventricles - metabolism
Heart Ventricles - pathology
Hogs
Humanities and Social Sciences
Hypertension
Hypertrophy
Living myocardial slices
Mechanical properties
MicroRNAs - genetics
MicroRNAs - metabolism
multidisciplinary
Muscle contraction
Myocardium
Myocardium - metabolism
Myocardium - pathology
Peptides
Physiology
Proteins
Public health
Science
Science (multidisciplinary)
Stress, Mechanical
Swine
TGF-β stimulation
Transforming Growth Factor beta1 - metabolism
Transforming Growth Factor beta1 - pharmacology
Transforming growth factor-b
Transforming growth factor-b1
Ventricular Remodeling
Living myocardial slices
Fibroblast activation
Cardiovascular diseases
Fibrosis
TGF-β stimulation
Hypertrophy
(up to 6): Cardiovascular diseases
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:Heart failure (HF) is a growing global health concern, driven by factors such as increased mechanical load of the heart muscle tissue. This pathogenic condition is the result of remodeling processes, partially mediated by the cytokine transforming growth factor β (TGF- β1), with progressive deposition of extracellular matrix within the myocardium that ultimately increases tissue stiffness. To elucidate early cellular and molecular processes underlying cardiac remodeling, translational experimental models are required. Living myocardial slices (LMS) represent a promising ex vivo model with preserved multicellularity, and physiology. In this study, we developed a disease model with hypertrophic and fibrotic features in porcine LMS. For this, LMS were prepared from porcine left ventricular tissue and cultured under mechanical overload with or without TGF-β1 stimulation. LMS cultured under overload showed reduced contractile performance, while adding TGF- β1 resulted in higher collagen deposition in the tissue, increase in secretion levels of pro-fibrotic miR-21 into the culture supernatant and increased expression of pro-fibrotic and hypertrophic marker genes. Our findings demonstrate early fibrotic changes in pig LMS induced by both mechanical and chemical stimulations. This ex vivo model could provide valuable insights into the early changes in heart failure pathogenesis and could be utilized as a screening platform to validate treatment strategies targeting cardiac remodeling.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-025-28222-z