Remodelling of adult cardiac tissue subjected to physiological and pathological mechanical load in vitro
| Autor: | Fotios G. Pitoulis, Ke Xiao, Raquel Nunez-Toldra, Thomas Thum, Saskia Mitzka, Richard J. Jabbour, Pieter P. de Tombe, Cesare M. Terracciano, Worrapong Kit-Anan, Filippo Perbellini, Sian E. Harding |
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| Přispěvatelé: | National Heart and Lung Institute [London] (NHLI), Royal Brompton and Harefield NHS Foundation Trust-Imperial College London, Medizinische Hochschule Hannover (MHH), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), British Heart Foundation |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pressure overload
Cardiac & Cardiovascular Systems Physiology Volume overload GOOD THERAPEUTIC STRATEGY Isometric exercise 030204 cardiovascular system & hematology Mechanical load Phosphatidylinositol 3-Kinases 0302 clinical medicine In vitro cardiac tissue culture [SPI.MECA.BIOM] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph] Medicine 1102 Cardiorespiratory Medicine and Haematology 0303 health sciences [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph] Heart DIASTOLIC DYSFUNCTION Myocardial remodelling [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Circulatory system [SDV.IB]Life Sciences [q-bio]/Bioengineering Cardiology and Cardiovascular Medicine Life Sciences & Biomedicine EXPRESSION VOLUME OVERLOAD 03 medical and health sciences Afterload [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system LEFT-VENTRICULAR FUNCTION In vivo Physiology (medical) MYOCARDIAL SLICES Animals AORTIC-STENOSIS 030304 developmental biology Heart Failure [SDV.IB] Life Sciences [q-bio]/Bioengineering Science & Technology HYPERTENSION business.industry Myocardium Myocardial Contraction Rats HYPERTROPHY Preload Cardiovascular System & Hematology Cardiovascular System & Cardiology business Biomedical engineering |
| Zdroj: | Cardiovascular Research Cardiovascular Research, Oxford University Press (OUP), In press, ⟨10.1093/cvr/cvab084⟩ Cardiovascular Research, In press, ⟨10.1093/cvr/cvab084⟩ |
| ISSN: | 0008-6363 |
| Popis: | Aims Cardiac remodelling is the process by which the heart adapts to its environment. Mechanical load is a major driver of remodelling. Cardiac tissue culture has been frequently employed for in vitro studies of load-induced remodelling; however, current in vitro protocols (e.g. cyclic stretch, isometric load, and auxotonic load) are oversimplified and do not accurately capture the dynamic sequence of mechanical conformational changes experienced by the heart in vivo. This limits translational scope and relevance of findings. Methods and results We developed a novel methodology to study chronic load in vitro. We first developed a bioreactor that can recreate the electromechanical events of in vivo pressure–volume loops as in vitro force–length loops. We then used the bioreactor to culture rat living myocardial slices (LMS) for 3 days. The bioreactor operated based on a 3-Element Windkessel circulatory model enabling tissue mechanical loading based on physiologically relevant parameters of afterload and preload. LMS were continuously stretched/relaxed during culture simulating conditions of physiological load (normal preload and afterload), pressure-overload (normal preload and high afterload), or volume-overload (high preload & normal afterload). At the end of culture, functional, structural, and molecular assays were performed to determine load-induced remodelling. Both pressure- and volume-overloaded LMS showed significantly decreased contractility that was more pronounced in the latter compared with physiological load (P Conclusion We have developed a proof-of-concept platform and methodology to recreate remodelling under pathophysiological load in vitro. We show that LMS cultured in our bioreactor remodel as a function of the type of mechanical load applied to them. |
| Databáze: | OpenAIRE |
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