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MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression

The cardiopathogenic role of autoantibodies (aabs) directed against β1-adrenoreceptors (β1-AR) is well established. In mouse models, they cause progressive dilated cardiomyopathy (DCM) whose characterization with echocardiography requires prolonged protocols with numerous animals, complicating the e...

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Autores principales: Vanhoutte, Laetitia, Guilbaud, Céline, Martherus, Ruben, Bouzin, Caroline, Gallez, Bernard, Dessy, Chantal, Balligand, Jean-Luc, Moniotte, Stéphane, Feron, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343428/
https://www.ncbi.nlm.nih.gov/pubmed/28276515
http://dx.doi.org/10.1038/srep43951
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author Vanhoutte, Laetitia
Guilbaud, Céline
Martherus, Ruben
Bouzin, Caroline
Gallez, Bernard
Dessy, Chantal
Balligand, Jean-Luc
Moniotte, Stéphane
Feron, Olivier
author_facet Vanhoutte, Laetitia
Guilbaud, Céline
Martherus, Ruben
Bouzin, Caroline
Gallez, Bernard
Dessy, Chantal
Balligand, Jean-Luc
Moniotte, Stéphane
Feron, Olivier
author_sort Vanhoutte, Laetitia
collection PubMed
description The cardiopathogenic role of autoantibodies (aabs) directed against β1-adrenoreceptors (β1-AR) is well established. In mouse models, they cause progressive dilated cardiomyopathy (DCM) whose characterization with echocardiography requires prolonged protocols with numerous animals, complicating the evaluation of new treatments. Here, we report on the characterization of β1-aabs-induced DCM in mice using 11.7T MRI. C57BL/6J mice (n = 10 per group) were immunized against the β1-AR and left ventricular (LV) systolic function was assessed at 10, 18 and 27 weeks. Increase in LV mass/tibial length ratio was detected as the first modification at 10 weeks together with dilation of cavities, thereby outperforming echocardiography. Significant impairment in diastolic index was also observed in immunized animals before the onset of systolic dysfunction. Morphometric and histological measurements confirmed these observations. The same protocol performed on β3-AR-overexpressing mice and wild-type littermates (n = 8–12 per group) showed that transgenic animals were protected with reduced LV/TL ratio compared to wild-type animals and maintenance of the diastolic index. This study demonstrates that MRI allows a precocious detection of the subtle myocardial dysfunction induced by β1-aabs and that β3-AR stimulation blunts the development of β1-aabs-induced DCM, thereby paving the way for the use of β3AR-stimulating drugs to treat this autoimmune cardiomyopathy.
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spelling pubmed-53434282017-03-14 MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression Vanhoutte, Laetitia Guilbaud, Céline Martherus, Ruben Bouzin, Caroline Gallez, Bernard Dessy, Chantal Balligand, Jean-Luc Moniotte, Stéphane Feron, Olivier Sci Rep Article The cardiopathogenic role of autoantibodies (aabs) directed against β1-adrenoreceptors (β1-AR) is well established. In mouse models, they cause progressive dilated cardiomyopathy (DCM) whose characterization with echocardiography requires prolonged protocols with numerous animals, complicating the evaluation of new treatments. Here, we report on the characterization of β1-aabs-induced DCM in mice using 11.7T MRI. C57BL/6J mice (n = 10 per group) were immunized against the β1-AR and left ventricular (LV) systolic function was assessed at 10, 18 and 27 weeks. Increase in LV mass/tibial length ratio was detected as the first modification at 10 weeks together with dilation of cavities, thereby outperforming echocardiography. Significant impairment in diastolic index was also observed in immunized animals before the onset of systolic dysfunction. Morphometric and histological measurements confirmed these observations. The same protocol performed on β3-AR-overexpressing mice and wild-type littermates (n = 8–12 per group) showed that transgenic animals were protected with reduced LV/TL ratio compared to wild-type animals and maintenance of the diastolic index. This study demonstrates that MRI allows a precocious detection of the subtle myocardial dysfunction induced by β1-aabs and that β3-AR stimulation blunts the development of β1-aabs-induced DCM, thereby paving the way for the use of β3AR-stimulating drugs to treat this autoimmune cardiomyopathy. Nature Publishing Group 2017-03-09 /pmc/articles/PMC5343428/ /pubmed/28276515 http://dx.doi.org/10.1038/srep43951 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Vanhoutte, Laetitia
Guilbaud, Céline
Martherus, Ruben
Bouzin, Caroline
Gallez, Bernard
Dessy, Chantal
Balligand, Jean-Luc
Moniotte, Stéphane
Feron, Olivier
MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression
title MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression
title_full MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression
title_fullStr MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression
title_full_unstemmed MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression
title_short MRI Assessment of Cardiomyopathy Induced by β1-Adrenoreceptor Autoantibodies and Protection Through β3-Adrenoreceptor Overexpression
title_sort mri assessment of cardiomyopathy induced by β1-adrenoreceptor autoantibodies and protection through β3-adrenoreceptor overexpression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343428/
https://www.ncbi.nlm.nih.gov/pubmed/28276515
http://dx.doi.org/10.1038/srep43951
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