SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice.

SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice.
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DOI:
10.1186/1479-5876-9-132
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发表时间:
2011-08-11
影响因子:
7.4
通讯作者:
Duan D
Duan D
中科院分区:
医学2区
文献类型:
--
作者:
Shin JH;Bostick B;Yue Y;Hajjar R;Duan D

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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. 1 × 1012 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. 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. Our results suggest that AAV SERCA2a therapy may hold great promise in treating dystrophin-deficient heart disease.
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发表时间: 2010-01-26
影响因子: 11.1
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期刊: MUSCLE GENE THERAPY: METHODS AND PROTOCOLS
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影响因子: 2.7
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发表时间: 2009-08
期刊: Cell calcium
影响因子: 4
作者:
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通讯作者: Niggli E