Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient?
Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is associated with reduced exercise capacity elicited by skeletal muscle (SM) alterations. Up to now, no clear medical treatment advice for HFpEF is available. Identification of the ideal animal model mimicking the human condition...
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Format: | Article |
Language: | English |
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Wiley
2021-02-01
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Series: | ESC Heart Failure |
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Online Access: | https://doi.org/10.1002/ehf2.13142 |
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doaj-2a3df83eb2a34f63b2b6fed167aefc45 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Keita Goto Antje Schauer Antje Augstein Mei Methawasin Henk Granzier Martin Halle Emeline M Van Craenenbroeck Natale Rolim Stephan Gielen Burkert Pieske Ephraim B. Winzer Axel Linke Volker Adams |
spellingShingle |
Keita Goto Antje Schauer Antje Augstein Mei Methawasin Henk Granzier Martin Halle Emeline M Van Craenenbroeck Natale Rolim Stephan Gielen Burkert Pieske Ephraim B. Winzer Axel Linke Volker Adams Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient? ESC Heart Failure Skeletal muscle Heart failure with preserved ejection fraction Animal models |
author_facet |
Keita Goto Antje Schauer Antje Augstein Mei Methawasin Henk Granzier Martin Halle Emeline M Van Craenenbroeck Natale Rolim Stephan Gielen Burkert Pieske Ephraim B. Winzer Axel Linke Volker Adams |
author_sort |
Keita Goto |
title |
Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient? |
title_short |
Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient? |
title_full |
Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient? |
title_fullStr |
Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient? |
title_full_unstemmed |
Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient? |
title_sort |
muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient? |
publisher |
Wiley |
series |
ESC Heart Failure |
issn |
2055-5822 |
publishDate |
2021-02-01 |
description |
Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is associated with reduced exercise capacity elicited by skeletal muscle (SM) alterations. Up to now, no clear medical treatment advice for HFpEF is available. Identification of the ideal animal model mimicking the human condition is a critical step in developing and testing treatment strategies. Several HFpEF animals have been described, but the most suitable in terms of comparability with SM alterations in HFpEF patients is unclear. The aim of the present study was to investigate molecular changes in SM of three different animal models and to compare them with alterations of muscle biopsies obtained from human HFpEF patients. Methods and results Skeletal muscle tissue was obtained from HFpEF and control patients and from three different animal models including the respective controls—ZSF1 rat, Dahl salt‐sensitive rat, and transverse aortic constriction surgery/deoxycorticosterone mouse. The development of HFpEF was verified by echocardiography. Protein expression and enzyme activity of selected markers were assessed in SM tissue homogenates. Protein expression between SM tissue obtained from HFpEF patients and the ZSF1 rats revealed similarities for protein markers involved in muscle atrophy (MuRF1 expression, protein ubiquitinylation, and LC3) and mitochondrial metabolism (succinate dehydrogenase and malate dehydrogenase activity, porin expression). The other two animal models exhibited far less similarities to the human samples. Conclusions None of the three tested animal models mimics the condition in HFpEF patients completely, but among the animal models tested, the ZSF1 rat (ZSF1‐lean vs. ZSF1‐obese) shows the highest overlap to the human condition. Therefore, when studying therapeutic interventions to treat HFpEF and especially alterations in the SM, we suggest that the ZSF1 rat is a suitable model. |
topic |
Skeletal muscle Heart failure with preserved ejection fraction Animal models |
url |
https://doi.org/10.1002/ehf2.13142 |
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doaj-2a3df83eb2a34f63b2b6fed167aefc452021-03-31T03:15:44ZengWileyESC Heart Failure2055-58222021-02-018113915010.1002/ehf2.13142Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient?Keita Goto0Antje Schauer1Antje Augstein2Mei Methawasin3Henk Granzier4Martin Halle5Emeline M Van Craenenbroeck6Natale Rolim7Stephan Gielen8Burkert Pieske9Ephraim B. Winzer10Axel Linke11Volker Adams12Laboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology TU Dresden, Heart Center Dresden University Hospital Fetscherstrasse 76 Dresden 01307 GermanyLaboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology TU Dresden, Heart Center Dresden University Hospital Fetscherstrasse 76 Dresden 01307 GermanyLaboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology TU Dresden, Heart Center Dresden University Hospital Fetscherstrasse 76 Dresden 01307 GermanyDepartment of Cellular and Molecular Medicine University of Arizona Tucson USADepartment of Cellular and Molecular Medicine University of Arizona Tucson USAPrevention and Sports Medicine, Klinikum rechts der Isar Technical University of Munich Munich GermanyResearch group Cardiovascular Diseases, GENCOR Department Antwerp University Hospital Edegem BelgiumDepartment of Circulation and Medical Imaging, Faculty of Medicine NTNU, K.G. Jebsen Center of Exercise in Medicine Trondheim NorwayDepartment of Cardiology, Angiology and Intensive Care Klinikum Lippe Detmold GermanyDepartment of Internal Medicine and Cardiology Campus Virchow‐Klinikum Charité—Universitätsmedizin Berlin Berlin GermanyLaboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology TU Dresden, Heart Center Dresden University Hospital Fetscherstrasse 76 Dresden 01307 GermanyLaboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology TU Dresden, Heart Center Dresden University Hospital Fetscherstrasse 76 Dresden 01307 GermanyLaboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology TU Dresden, Heart Center Dresden University Hospital Fetscherstrasse 76 Dresden 01307 GermanyAbstract Aims Heart failure with preserved ejection fraction (HFpEF) is associated with reduced exercise capacity elicited by skeletal muscle (SM) alterations. Up to now, no clear medical treatment advice for HFpEF is available. Identification of the ideal animal model mimicking the human condition is a critical step in developing and testing treatment strategies. Several HFpEF animals have been described, but the most suitable in terms of comparability with SM alterations in HFpEF patients is unclear. The aim of the present study was to investigate molecular changes in SM of three different animal models and to compare them with alterations of muscle biopsies obtained from human HFpEF patients. Methods and results Skeletal muscle tissue was obtained from HFpEF and control patients and from three different animal models including the respective controls—ZSF1 rat, Dahl salt‐sensitive rat, and transverse aortic constriction surgery/deoxycorticosterone mouse. The development of HFpEF was verified by echocardiography. Protein expression and enzyme activity of selected markers were assessed in SM tissue homogenates. Protein expression between SM tissue obtained from HFpEF patients and the ZSF1 rats revealed similarities for protein markers involved in muscle atrophy (MuRF1 expression, protein ubiquitinylation, and LC3) and mitochondrial metabolism (succinate dehydrogenase and malate dehydrogenase activity, porin expression). The other two animal models exhibited far less similarities to the human samples. Conclusions None of the three tested animal models mimics the condition in HFpEF patients completely, but among the animal models tested, the ZSF1 rat (ZSF1‐lean vs. ZSF1‐obese) shows the highest overlap to the human condition. Therefore, when studying therapeutic interventions to treat HFpEF and especially alterations in the SM, we suggest that the ZSF1 rat is a suitable model.https://doi.org/10.1002/ehf2.13142Skeletal muscleHeart failure with preserved ejection fractionAnimal models |