title: 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.
abstract: 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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Agrawal
authors.forename: S
authors.initials: S
authors.lastname: Muangman
authors.forename: M D
authors.initials: MD
authors.lastname: Layne
authors.forename: L
authors.initials: L
authors.lastname: Melo
authors.forename: M A
authors.initials: MA
authors.lastname: Perrella
authors.forename: R T
authors.initials: RT
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Lopez-Ilasaca
authors.forename: V J
authors.initials: VJ
authors.lastname: Dzau
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D045604:Extracellular Fluid / Q000201:enzymology; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy; D015428:Myocardial Reperfusion Injury / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics*; D015996:Survival Rate; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods*; D016276:Ventricular Function
chemical_list: D013482:Superoxide Dismutase