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Pre-emptive gene therapy using recombinant adeno-associated virus delivery of extracellular superoxide dismutase protects heart against ischemic reperfusion injury, improves ventricular function and prolongs survival.

Publication ,  Journal Article
Agrawal, RS; Muangman, S; Layne, MD; Melo, L; Perrella, MA; Lee, RT; Zhang, L; Lopez-Ilasaca, M; Dzau, VJ
Published in: Gene Ther
June 2004

In high-risk patients, the ideal cardiovascular gene therapy requires a strategy that provides long-term protection of myocardium against episodes of ischemic/reperfusion injury. We report the development of an efficient, long-lasting pre-emptive gene therapy strategy in a rat model of ischemic-reperfusion (I/R) injury of heart. At 6 weeks prior to myocardial injury, the human extracellular superoxide dismutase (Ec-SOD) gene was delivered by direct intramyocardial injections, using a recombinant adeno-associated virus vector. Significant myocardial protection was documented by the decrease in infarct size at 24 h post I/R, improved left ventricular function at 7 weeks postinjury, and enhanced long-term survival in the SOD treated group. This concept of preinjury delivery and 'pre-emptive' gene therapy via the expression of a secreted protein that renders paracrine therapeutic action can be an effective strategy for organ protection against future injury.

Duke Scholars

Published In

Gene Ther

DOI

ISSN

0969-7128

Publication Date

June 2004

Volume

11

Issue

12

Start / End Page

962 / 969

Location

England

Related Subject Headings

  • Ventricular Function
  • Transduction, Genetic
  • Time Factors
  • Survival Rate
  • Superoxide Dismutase
  • Rats, Sprague-Dawley
  • Rats
  • Myocardium
  • Myocardial Reperfusion Injury
  • Myocardial Infarction
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Agrawal, R. S., Muangman, S., Layne, M. D., Melo, L., Perrella, M. A., Lee, R. T., … Dzau, V. J. (2004). Pre-emptive gene therapy using recombinant adeno-associated virus delivery of extracellular superoxide dismutase protects heart against ischemic reperfusion injury, improves ventricular function and prolongs survival. Gene Ther, 11(12), 962–969. https://doi.org/10.1038/sj.gt.3302250
Agrawal, R. S., S. Muangman, M. D. Layne, L. Melo, M. A. Perrella, R. T. Lee, L. Zhang, M. Lopez-Ilasaca, and V. J. Dzau. “Pre-emptive gene therapy using recombinant adeno-associated virus delivery of extracellular superoxide dismutase protects heart against ischemic reperfusion injury, improves ventricular function and prolongs survival.Gene Ther 11, no. 12 (June 2004): 962–69. https://doi.org/10.1038/sj.gt.3302250.

Published In

Gene Ther

DOI

ISSN

0969-7128

Publication Date

June 2004

Volume

11

Issue

12

Start / End Page

962 / 969

Location

England

Related Subject Headings

  • Ventricular Function
  • Transduction, Genetic
  • Time Factors
  • Survival Rate
  • Superoxide Dismutase
  • Rats, Sprague-Dawley
  • Rats
  • Myocardium
  • Myocardial Reperfusion Injury
  • Myocardial Infarction