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Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study

BACKGROUND: Animal studies demonstrated that serelaxin lessens fibrosis in heart failure. This study assessed its effect on myocardial deformation using cardiac magnetic resonance and elucidated its relationship to gene regulation and histology in a mouse heart failure model. METHODS AND RESULTS: C5...

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Autores principales: Lapinskas, Tomas, Kelle, Sebastian, Grune, Jana, Foryst‐Ludwig, Anna, Meyborg, Heike, Jeuthe, Sarah, Wellnhofer, Ernst, Elsanhoury, Ahmed, Pieske, Burkert, Gebker, Rolf, Kintscher, Ulrich, Stawowy, Philipp
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033894/
https://www.ncbi.nlm.nih.gov/pubmed/32000566
http://dx.doi.org/10.1161/JAHA.119.013702
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author Lapinskas, Tomas
Kelle, Sebastian
Grune, Jana
Foryst‐Ludwig, Anna
Meyborg, Heike
Jeuthe, Sarah
Wellnhofer, Ernst
Elsanhoury, Ahmed
Pieske, Burkert
Gebker, Rolf
Kintscher, Ulrich
Stawowy, Philipp
author_facet Lapinskas, Tomas
Kelle, Sebastian
Grune, Jana
Foryst‐Ludwig, Anna
Meyborg, Heike
Jeuthe, Sarah
Wellnhofer, Ernst
Elsanhoury, Ahmed
Pieske, Burkert
Gebker, Rolf
Kintscher, Ulrich
Stawowy, Philipp
author_sort Lapinskas, Tomas
collection PubMed
description BACKGROUND: Animal studies demonstrated that serelaxin lessens fibrosis in heart failure. This study assessed its effect on myocardial deformation using cardiac magnetic resonance and elucidated its relationship to gene regulation and histology in a mouse heart failure model. METHODS AND RESULTS: C57BL/6J mice were subjected to SHAM (n=4) or transverse aortic constriction (TAC). At week 10, TAC mice were randomized to receive either serelaxin (0.5 mg/kg per day; n=11) or vehicle (n=13) for 4 weeks. Cardiac magnetic resonance imaging was performed at baseline and repeated at the end of the study (week 14). Cine images were used to calculate left ventricular (LV) global longitudinal, circumferential, and radial strain. Hearts were examined for histology and gene expression. Compared with SHAM, mice 10 weeks after TAC showed increased LV mass with significant decreases in LV deformation parameters, indicating subclinical deterioration of myocardial function. At week 14, TAC mice given serelaxin demonstrated significant improvements in all LV strain parameters and no decrease in LV stroke volume and ejection fraction compared with TAC mice given vehicle. A significant positive correlation between global circumferential strain and the extent of myocardial fibrosis was found, and global circumferential strain correlated significantly with the expression of heart failure genes in serelaxin‐treated mice. CONCLUSIONS: Serelaxin improved cardiac magnetic resonance–derived myocardial deformation parameters as well as histomorphometric and gene expression findings in mice with heart failure. Cardiac magnetic resonance–derived myocardial mechanics correlate with histology and gene expression, stressing its utilization in myocardial remodeling.
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spelling pubmed-70338942020-02-27 Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study Lapinskas, Tomas Kelle, Sebastian Grune, Jana Foryst‐Ludwig, Anna Meyborg, Heike Jeuthe, Sarah Wellnhofer, Ernst Elsanhoury, Ahmed Pieske, Burkert Gebker, Rolf Kintscher, Ulrich Stawowy, Philipp J Am Heart Assoc Original Research BACKGROUND: Animal studies demonstrated that serelaxin lessens fibrosis in heart failure. This study assessed its effect on myocardial deformation using cardiac magnetic resonance and elucidated its relationship to gene regulation and histology in a mouse heart failure model. METHODS AND RESULTS: C57BL/6J mice were subjected to SHAM (n=4) or transverse aortic constriction (TAC). At week 10, TAC mice were randomized to receive either serelaxin (0.5 mg/kg per day; n=11) or vehicle (n=13) for 4 weeks. Cardiac magnetic resonance imaging was performed at baseline and repeated at the end of the study (week 14). Cine images were used to calculate left ventricular (LV) global longitudinal, circumferential, and radial strain. Hearts were examined for histology and gene expression. Compared with SHAM, mice 10 weeks after TAC showed increased LV mass with significant decreases in LV deformation parameters, indicating subclinical deterioration of myocardial function. At week 14, TAC mice given serelaxin demonstrated significant improvements in all LV strain parameters and no decrease in LV stroke volume and ejection fraction compared with TAC mice given vehicle. A significant positive correlation between global circumferential strain and the extent of myocardial fibrosis was found, and global circumferential strain correlated significantly with the expression of heart failure genes in serelaxin‐treated mice. CONCLUSIONS: Serelaxin improved cardiac magnetic resonance–derived myocardial deformation parameters as well as histomorphometric and gene expression findings in mice with heart failure. Cardiac magnetic resonance–derived myocardial mechanics correlate with histology and gene expression, stressing its utilization in myocardial remodeling. John Wiley and Sons Inc. 2020-01-31 /pmc/articles/PMC7033894/ /pubmed/32000566 http://dx.doi.org/10.1161/JAHA.119.013702 Text en © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Lapinskas, Tomas
Kelle, Sebastian
Grune, Jana
Foryst‐Ludwig, Anna
Meyborg, Heike
Jeuthe, Sarah
Wellnhofer, Ernst
Elsanhoury, Ahmed
Pieske, Burkert
Gebker, Rolf
Kintscher, Ulrich
Stawowy, Philipp
Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study
title Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study
title_full Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study
title_fullStr Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study
title_full_unstemmed Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study
title_short Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study
title_sort serelaxin improves regional myocardial function in experimental heart failure: an in vivo cardiac magnetic resonance study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033894/
https://www.ncbi.nlm.nih.gov/pubmed/32000566
http://dx.doi.org/10.1161/JAHA.119.013702
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