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Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart

Duchenne muscular dystrophy (DMD) is a devastating condition shortening the lifespan of young men. DMD patients suffer from age-related dilated cardiomyopathy (DCM) that leads to heart failure. Several molecular mechanisms leading to cardiomyocyte death in DMD have been described. However, the patho...

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Autores principales: Jelinkova, Sarka, Sleiman, Yvonne, Fojtík, Petr, Aimond, Franck, Finan, Amanda, Hugon, Gerald, Scheuermann, Valerie, Beckerová, Deborah, Cazorla, Olivier, Vincenti, Marie, Amedro, Pascal, Richard, Sylvain, Jaros, Josef, Dvorak, Petr, Lacampagne, Alain, Carnac, Gilles, Rotrekl, Vladimir, Meli, Albano C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125982/
https://www.ncbi.nlm.nih.gov/pubmed/34068508
http://dx.doi.org/10.3390/ijms22095025
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author Jelinkova, Sarka
Sleiman, Yvonne
Fojtík, Petr
Aimond, Franck
Finan, Amanda
Hugon, Gerald
Scheuermann, Valerie
Beckerová, Deborah
Cazorla, Olivier
Vincenti, Marie
Amedro, Pascal
Richard, Sylvain
Jaros, Josef
Dvorak, Petr
Lacampagne, Alain
Carnac, Gilles
Rotrekl, Vladimir
Meli, Albano C.
author_facet Jelinkova, Sarka
Sleiman, Yvonne
Fojtík, Petr
Aimond, Franck
Finan, Amanda
Hugon, Gerald
Scheuermann, Valerie
Beckerová, Deborah
Cazorla, Olivier
Vincenti, Marie
Amedro, Pascal
Richard, Sylvain
Jaros, Josef
Dvorak, Petr
Lacampagne, Alain
Carnac, Gilles
Rotrekl, Vladimir
Meli, Albano C.
author_sort Jelinkova, Sarka
collection PubMed
description Duchenne muscular dystrophy (DMD) is a devastating condition shortening the lifespan of young men. DMD patients suffer from age-related dilated cardiomyopathy (DCM) that leads to heart failure. Several molecular mechanisms leading to cardiomyocyte death in DMD have been described. However, the pathological progression of DMD-associated DCM remains unclear. In skeletal muscle, a dramatic decrease in stem cells, so-called satellite cells, has been shown in DMD patients. Whether similar dysfunction occurs with cardiac muscle cardiovascular progenitor cells (CVPCs) in DMD remains to be explored. We hypothesized that the number of CVPCs decreases in the dystrophin-deficient heart with age and disease state, contributing to DCM progression. We used the dystrophin-deficient mouse model (mdx) to investigate age-dependent CVPC properties. Using quantitative PCR, flow cytometry, speckle tracking echocardiography, and immunofluorescence, we revealed that young mdx mice exhibit elevated CVPCs. We observed a rapid age-related CVPC depletion, coinciding with the progressive onset of cardiac dysfunction. Moreover, mdx CVPCs displayed increased DNA damage, suggesting impaired cardiac muscle homeostasis. Overall, our results identify the early recruitment of CVPCs in dystrophic hearts and their fast depletion with ageing. This latter depletion may participate in the fibrosis development and the acceleration onset of the cardiomyopathy.
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spelling pubmed-81259822021-05-17 Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart Jelinkova, Sarka Sleiman, Yvonne Fojtík, Petr Aimond, Franck Finan, Amanda Hugon, Gerald Scheuermann, Valerie Beckerová, Deborah Cazorla, Olivier Vincenti, Marie Amedro, Pascal Richard, Sylvain Jaros, Josef Dvorak, Petr Lacampagne, Alain Carnac, Gilles Rotrekl, Vladimir Meli, Albano C. Int J Mol Sci Article Duchenne muscular dystrophy (DMD) is a devastating condition shortening the lifespan of young men. DMD patients suffer from age-related dilated cardiomyopathy (DCM) that leads to heart failure. Several molecular mechanisms leading to cardiomyocyte death in DMD have been described. However, the pathological progression of DMD-associated DCM remains unclear. In skeletal muscle, a dramatic decrease in stem cells, so-called satellite cells, has been shown in DMD patients. Whether similar dysfunction occurs with cardiac muscle cardiovascular progenitor cells (CVPCs) in DMD remains to be explored. We hypothesized that the number of CVPCs decreases in the dystrophin-deficient heart with age and disease state, contributing to DCM progression. We used the dystrophin-deficient mouse model (mdx) to investigate age-dependent CVPC properties. Using quantitative PCR, flow cytometry, speckle tracking echocardiography, and immunofluorescence, we revealed that young mdx mice exhibit elevated CVPCs. We observed a rapid age-related CVPC depletion, coinciding with the progressive onset of cardiac dysfunction. Moreover, mdx CVPCs displayed increased DNA damage, suggesting impaired cardiac muscle homeostasis. Overall, our results identify the early recruitment of CVPCs in dystrophic hearts and their fast depletion with ageing. This latter depletion may participate in the fibrosis development and the acceleration onset of the cardiomyopathy. MDPI 2021-05-10 /pmc/articles/PMC8125982/ /pubmed/34068508 http://dx.doi.org/10.3390/ijms22095025 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jelinkova, Sarka
Sleiman, Yvonne
Fojtík, Petr
Aimond, Franck
Finan, Amanda
Hugon, Gerald
Scheuermann, Valerie
Beckerová, Deborah
Cazorla, Olivier
Vincenti, Marie
Amedro, Pascal
Richard, Sylvain
Jaros, Josef
Dvorak, Petr
Lacampagne, Alain
Carnac, Gilles
Rotrekl, Vladimir
Meli, Albano C.
Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart
title Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart
title_full Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart
title_fullStr Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart
title_full_unstemmed Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart
title_short Dystrophin Deficiency Causes Progressive Depletion of Cardiovascular Progenitor Cells in the Heart
title_sort dystrophin deficiency causes progressive depletion of cardiovascular progenitor cells in the heart
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125982/
https://www.ncbi.nlm.nih.gov/pubmed/34068508
http://dx.doi.org/10.3390/ijms22095025
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