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SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice

BACKGROUND: Cardiomyocyte calcium overloading has been implicated in the pathogenesis of Duchenne muscular dystrophy (DMD) heart disease. The cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a major role in removing cytosolic calcium during heart muscle relaxation. Here, we t...

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Autores principales: Shin, Jin-Hong, Bostick, Brian, Yue, Yongping, Hajjar, Roger, Duan, Dongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162513/
https://www.ncbi.nlm.nih.gov/pubmed/21834967
http://dx.doi.org/10.1186/1479-5876-9-132
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author Shin, Jin-Hong
Bostick, Brian
Yue, Yongping
Hajjar, Roger
Duan, Dongsheng
author_facet Shin, Jin-Hong
Bostick, Brian
Yue, Yongping
Hajjar, Roger
Duan, Dongsheng
author_sort Shin, Jin-Hong
collection PubMed
description BACKGROUND: Cardiomyocyte calcium overloading has been implicated in the pathogenesis of Duchenne muscular dystrophy (DMD) heart disease. The cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a major role in removing cytosolic calcium during heart muscle relaxation. Here, we tested the hypothesis that SERCA2a over-expression may mitigate electrocardiography (ECG) abnormalities in old female mdx mice, a murine model of DMD cardiomyopathy. METHODS: 1 × 10(12 )viral genome particles/mouse of adeno-associated virus serotype-9 (AAV-9) SERCA2a vector was delivered to 12-m-old female mdx mice (N = 5) via a single bolus tail vein injection. AAV transduction and the ECG profile were examined eight months later. RESULTS: The vector genome was detected in the hearts of all AAV-injected mdx mice. Immunofluorescence staining and western blot confirmed SERCA2a over-expression in the mdx heart. Untreated mdx mice showed characteristic tachycardia, PR interval reduction and QT interval prolongation. AAV-9 SERCA2a treatment corrected these ECG abnormalities. CONCLUSIONS: Our results suggest that AAV SERCA2a therapy may hold great promise in treating dystrophin-deficient heart disease.
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spelling pubmed-31625132011-08-27 SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice Shin, Jin-Hong Bostick, Brian Yue, Yongping Hajjar, Roger Duan, Dongsheng J Transl Med Research BACKGROUND: Cardiomyocyte calcium overloading has been implicated in the pathogenesis of Duchenne muscular dystrophy (DMD) heart disease. The cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a major role in removing cytosolic calcium during heart muscle relaxation. Here, we tested the hypothesis that SERCA2a over-expression may mitigate electrocardiography (ECG) abnormalities in old female mdx mice, a murine model of DMD cardiomyopathy. METHODS: 1 × 10(12 )viral genome particles/mouse of adeno-associated virus serotype-9 (AAV-9) SERCA2a vector was delivered to 12-m-old female mdx mice (N = 5) via a single bolus tail vein injection. AAV transduction and the ECG profile were examined eight months later. RESULTS: The vector genome was detected in the hearts of all AAV-injected mdx mice. Immunofluorescence staining and western blot confirmed SERCA2a over-expression in the mdx heart. Untreated mdx mice showed characteristic tachycardia, PR interval reduction and QT interval prolongation. AAV-9 SERCA2a treatment corrected these ECG abnormalities. CONCLUSIONS: Our results suggest that AAV SERCA2a therapy may hold great promise in treating dystrophin-deficient heart disease. BioMed Central 2011-08-11 /pmc/articles/PMC3162513/ /pubmed/21834967 http://dx.doi.org/10.1186/1479-5876-9-132 Text en Copyright ©2011 Shin et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Shin, Jin-Hong
Bostick, Brian
Yue, Yongping
Hajjar, Roger
Duan, Dongsheng
SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice
title SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice
title_full SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice
title_fullStr SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice
title_full_unstemmed SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice
title_short SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice
title_sort serca2a gene transfer improves electrocardiographic performance in aged mdx mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162513/
https://www.ncbi.nlm.nih.gov/pubmed/21834967
http://dx.doi.org/10.1186/1479-5876-9-132
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