PMID- 21674736
OWN - NLM
STAT- MEDLINE
DCOM- 20111104
LR  - 20220316
IS  - 1521-2254 (Electronic)
IS  - 1099-498X (Print)
IS  - 1099-498X (Linking)
VI  - 13
IP  - 6
DP  - 2011 Jun
TI  - A single direct injection into the left ventricular wall of an adeno-associated 
      virus 9 (AAV9) vector expressing extracellular superoxide dismutase from the 
      cardiac troponin-T promoter protects mice against myocardial infarction.
PG  - 333-41
LID - 10.1002/jgm.1576 [doi]
AB  - BACKGROUND: Localized administration of a highly efficient gene delivery system 
      in combination with a cardiac-selective promoter may provide a favorable 
      biosafety profile in clinical applications such as coronary artery bypass graft 
      surgery, where regions of myocardium can be readily injected to protect them 
      against the potential threat of future ischemic events. METHODS: Adeno-associated 
      virus (AAV) vectors expressing luciferase or enhanced green fluorescent protein 
      (eGFP) packaged into AAV serotypes 1, 2, 6, 8 and 9 were injected into the left 
      ventricular (LV) wall of adult mice to determine the time course, magnitude and 
      distribution of gene expression. An AAV9 vector expressing extracellular 
      superoxide dismutase (EcSOD) from the cardiac troponin T (cTnT) promoter was then 
      directly injected into the LV wall of adult mice. Myocardial infarction was 
      induced 4 weeks after injection and infarct size was determined by 
      triphenyltetrazolium chloride and phthalo blue staining. RESULTS: Serotypes AAV 
      9, 8, 1 and 6 provided early onset of gene expression in the heart with minimal 
      extra-cardiac gene expression. AAV9 provided the highest magnitude of gene 
      expression. Immunostaining for eGFP showed expression spanning the anterior to 
      posterior walls from the mid ventricle to the apex. A single direct injection of 
      the AAV9 vector bearing EcSOD ( n  = 5) decreased the mean infarct size by 50% 
      compared to the eGFP control group (n = 8) (44 +/- 7% versus 22 +/- 5%; p = 0.04). 
      CONCLUSIONS: AAV serotype 9 is highly efficient for cardiac gene delivery, as 
      evidenced by early onset and high-level gene expression. AAV9-mediated, cardiac 
      selective overexpression of EcSOD from the cTnT promoter significantly reduced 
      infarct size in mice.
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Prasad, Konkal-Matt R
AU  - Prasad KM
AD  - Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 
      22903, USA.
FAU - Smith, Robert S
AU  - Smith RS
FAU - Xu, Yaqin
AU  - Xu Y
FAU - French, Brent A
AU  - French BA
LA  - eng
GR  - R01 HL058582/HL/NHLBI NIH HHS/United States
GR  - R01 HL092305/HL/NHLBI NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Troponin T)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents
MH  - Dependovirus/metabolism
MH  - Fluorescence
MH  - Gene Expression Regulation, Enzymologic/genetics/*physiology
MH  - *Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/administration & dosage
MH  - Heart Ventricles/*metabolism
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Luciferases
MH  - Mice
MH  - Myocardial Infarction/*enzymology/pathology/*prevention & control
MH  - Promoter Regions, Genetic/genetics
MH  - Superoxide Dismutase/genetics/*metabolism
MH  - Troponin T/genetics
PMC - PMC3984922
MID - NIHMS565424
EDAT- 2011/06/16 06:00
MHDA- 2011/11/05 06:00
PMCR- 2014/04/13
CRDT- 2011/06/16 06:00
PHST- 2011/06/16 06:00 [entrez]
PHST- 2011/06/16 06:00 [pubmed]
PHST- 2011/11/05 06:00 [medline]
PHST- 2014/04/13 00:00 [pmc-release]
AID - 10.1002/jgm.1576 [doi]
PST - ppublish
SO  - J Gene Med. 2011 Jun;13(6):333-41. doi: 10.1002/jgm.1576.