PMID- 21834967
OWN - NLM
STAT- MEDLINE
DCOM- 20111122
LR  - 20211020
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 9
DP  - 2011 Aug 11
TI  - SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice.
PG  - 132
LID - 10.1186/1479-5876-9-132 [doi]
AB  - 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 x 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.
FAU - Shin, Jin-Hong
AU  - Shin JH
AD  - Department of Molecular Microbiology and Immunology, School of Medicine, The 
      University of Missouri, Columbia, MO, USA.
FAU - Bostick, Brian
AU  - Bostick B
FAU - Yue, Yongping
AU  - Yue Y
FAU - Hajjar, Roger
AU  - Hajjar R
FAU - Duan, Dongsheng
AU  - Duan D
LA  - eng
GR  - R01 HL091883/HL/NHLBI NIH HHS/United States
GR  - HL91883/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110811
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
SB  - IM
MH  - Aging/*pathology
MH  - Animals
MH  - Dependovirus/genetics
MH  - *Electrocardiography
MH  - Female
MH  - *Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Mice
MH  - Mice, Inbred mdx
MH  - Myocardium/metabolism/pathology
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/*genetics/*therapeutic use
MH  - Transduction, Genetic
PMC - PMC3162513
EDAT- 2011/08/13 06:00
MHDA- 2011/12/13 00:00
PMCR- 2011/08/11
CRDT- 2011/08/13 06:00
PHST- 2011/04/06 00:00 [received]
PHST- 2011/08/11 00:00 [accepted]
PHST- 2011/08/13 06:00 [entrez]
PHST- 2011/08/13 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2011/08/11 00:00 [pmc-release]
AID - 1479-5876-9-132 [pii]
AID - 10.1186/1479-5876-9-132 [doi]
PST - epublish
SO  - J Transl Med. 2011 Aug 11;9:132. doi: 10.1186/1479-5876-9-132.