SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice
1 Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, MO, USA
2 Department of Cardiology, Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, USA
Journal of Translational Medicine 2011, 9:132 doi:10.1186/1479-5876-9-132Published: 11 August 2011
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.