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Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor

BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue. In some cases, myocardial injury secondary to hypoxia can lead to dilative cardiomyopathy (DCM). A genetic defect in the dystrophin gene may increase the suscept...

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Autores principales: Nowak, Dariusz, Kozlowska, Hanna, Gielecki, Jerzy S., Rowinski, Jan, Zurada, Anna, Goralczyk, Krzysztof, Bozilow, Wladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539494/
https://www.ncbi.nlm.nih.gov/pubmed/22037736
http://dx.doi.org/10.12659/MSM.882043
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author Nowak, Dariusz
Kozlowska, Hanna
Gielecki, Jerzy S.
Rowinski, Jan
Zurada, Anna
Goralczyk, Krzysztof
Bozilow, Wladimir
author_facet Nowak, Dariusz
Kozlowska, Hanna
Gielecki, Jerzy S.
Rowinski, Jan
Zurada, Anna
Goralczyk, Krzysztof
Bozilow, Wladimir
author_sort Nowak, Dariusz
collection PubMed
description BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue. In some cases, myocardial injury secondary to hypoxia can lead to dilative cardiomyopathy (DCM). A genetic defect in the dystrophin gene may increase the susceptibility of myocardium to hypoxia. Available data suggest that this may be caused by impaired secretion of NO, which is bound with secretion of VEGF-A. MATERIAL/METHODS: Male mice C57BI/10ScSn mdx (animal model of DMD) and healthy mice C57BI/10ScSn were exposed to hypobaric hypoxia in low-pressure chambers. Their hearts were harvested immediately after and 1, 3, 7, and 21 days after exposure to hypoxia. Normobaric mice were used as controls. The expression of VEGF-A in myocardium and cardiac vessel walls was evaluated using immunohistochemistry, Western blotting, and in situ hybridization. RESULTS: VEGF-A expression in myocardium and vessel walls of healthy mice peaked 24 hours after exposure to hypoxia. The expression of VEGF-A in vessel walls was similar in dystrophic and healthy mice; however, VEGF-A expression in the myocardium of dystrophic mice was impaired, peaking around day 7. In the heart, the total level of VEGF depends on VEGF expression in myocardium, not in vessel endothelium, and our research demonstrates that the expression of VEGF is dystrophin-dependent. CONCLUSIONS: Disordered secretion of VEGF-A in hypoxic myocardium caused the total level of this factor to be impaired in the heart. This factor, which in normal situations protect against hypoxia, promotes the gradual progression of cardiomyopathy.
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spelling pubmed-35394942013-04-24 Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor Nowak, Dariusz Kozlowska, Hanna Gielecki, Jerzy S. Rowinski, Jan Zurada, Anna Goralczyk, Krzysztof Bozilow, Wladimir Med Sci Monit Basic Research BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue. In some cases, myocardial injury secondary to hypoxia can lead to dilative cardiomyopathy (DCM). A genetic defect in the dystrophin gene may increase the susceptibility of myocardium to hypoxia. Available data suggest that this may be caused by impaired secretion of NO, which is bound with secretion of VEGF-A. MATERIAL/METHODS: Male mice C57BI/10ScSn mdx (animal model of DMD) and healthy mice C57BI/10ScSn were exposed to hypobaric hypoxia in low-pressure chambers. Their hearts were harvested immediately after and 1, 3, 7, and 21 days after exposure to hypoxia. Normobaric mice were used as controls. The expression of VEGF-A in myocardium and cardiac vessel walls was evaluated using immunohistochemistry, Western blotting, and in situ hybridization. RESULTS: VEGF-A expression in myocardium and vessel walls of healthy mice peaked 24 hours after exposure to hypoxia. The expression of VEGF-A in vessel walls was similar in dystrophic and healthy mice; however, VEGF-A expression in the myocardium of dystrophic mice was impaired, peaking around day 7. In the heart, the total level of VEGF depends on VEGF expression in myocardium, not in vessel endothelium, and our research demonstrates that the expression of VEGF is dystrophin-dependent. CONCLUSIONS: Disordered secretion of VEGF-A in hypoxic myocardium caused the total level of this factor to be impaired in the heart. This factor, which in normal situations protect against hypoxia, promotes the gradual progression of cardiomyopathy. International Scientific Literature, Inc. 2011-11-01 /pmc/articles/PMC3539494/ /pubmed/22037736 http://dx.doi.org/10.12659/MSM.882043 Text en © Med Sci Monit, 2011 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.
spellingShingle Basic Research
Nowak, Dariusz
Kozlowska, Hanna
Gielecki, Jerzy S.
Rowinski, Jan
Zurada, Anna
Goralczyk, Krzysztof
Bozilow, Wladimir
Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor
title Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor
title_full Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor
title_fullStr Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor
title_full_unstemmed Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor
title_short Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor
title_sort cardiomyopathy in the mouse model of duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor
topic Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539494/
https://www.ncbi.nlm.nih.gov/pubmed/22037736
http://dx.doi.org/10.12659/MSM.882043
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