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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Vydané v:	Scientific reports Ročník 15; číslo 1; s. 41180 - 14
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 21.11.2025 Nature Publishing Group Nature Portfolio
Predmet:	(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
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-025-28222-z