Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction

Qianhong Li, Roberto Bolli, Yumin Qiu, Xian Liang Tang, Yiru Guo, Brent A. French

Research output: Contribution to journalArticle

Abstract

Background - Extracellular superoxide dismutase (Ec-SOD) may protect the heart against myocardial infarction (MI) because of its extended half-life and capacity to bind heparan sulfate proteoglycans on cellular surfaces. Accordingly, we used direct gene transfer to increase systemic levels of Ec-SOD and determined whether this gene therapy could protect against MI. Methods and Results - The cDNA for human Ec-SOD was incorporated into a replication-deficient adenovirus (Ad5/CMV/Ec-SOD). Injection of this virus produced a high level of Ec-SOD in the liver, which was redistributed to the heart and other organs by injection of heparin. Untreated rabbits (group I) underwent a 30-minute coronary occlusion and 3 days of reperfusion. For comparison, preconditioned rabbits (group II) underwent a sequence of six 4-minute-occlusion/4-minute-reperfusion cycles 24 hours before the 30-minute occlusion. Control-treated rabbits (group III) were injected intravenously with Ad5/CMV/nls-LacZ, and gene-therapy rabbits (group IV) were injected with Ad5/CMV/Ec-SOD 3 days before the 30-minute occlusion. Both groups treated with Ad5 received intravenous heparin 2 hours before the 30-minute occlusion. Infarct size (percent risk area) was similar in groups I (57±6%) and III (58±5%). Ec-SOD gene therapy markedly reduced infarct size to 25±4% (P

Original languageEnglish (US)
Pages (from-to)1893-1898
Number of pages6
JournalCirculation
Volume103
Issue number14
StatePublished - Apr 10 2001
Externally publishedYes

Fingerprint

Genetic Therapy
Superoxide Dismutase
Myocardial Infarction
Rabbits
Reperfusion
Heparin
Heparan Sulfate Proteoglycans
Injections
Lac Operon
Coronary Occlusion
Adenoviridae
Half-Life
Complementary DNA
Viruses
Liver
Genes

Keywords

  • Antioxidants
  • Genes
  • Ischemia
  • Myocardial infarction
  • Viruses

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Li, Q., Bolli, R., Qiu, Y., Tang, X. L., Guo, Y., & French, B. A. (2001). Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. Circulation, 103(14), 1893-1898.

Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. / Li, Qianhong; Bolli, Roberto; Qiu, Yumin; Tang, Xian Liang; Guo, Yiru; French, Brent A.

In: Circulation, Vol. 103, No. 14, 10.04.2001, p. 1893-1898.

Research output: Contribution to journalArticle

Li, Q, Bolli, R, Qiu, Y, Tang, XL, Guo, Y & French, BA 2001, 'Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction', Circulation, vol. 103, no. 14, pp. 1893-1898.
Li Q, Bolli R, Qiu Y, Tang XL, Guo Y, French BA. Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. Circulation. 2001 Apr 10;103(14):1893-1898.
Li, Qianhong ; Bolli, Roberto ; Qiu, Yumin ; Tang, Xian Liang ; Guo, Yiru ; French, Brent A. / Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. In: Circulation. 2001 ; Vol. 103, No. 14. pp. 1893-1898.
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