title: SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, MO, USA.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Shin
authors.forename: Brian
authors.initials: B
authors.lastname: Bostick
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yue
authors.forename: Roger
authors.initials: R
authors.lastname: Hajjar
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Duan
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D000229:Dependovirus / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000627:therapeutic use*; D014161:Transduction, Genetic
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases