| Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. | |
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MedLine Citation:
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PMID: 11294809 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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<0.01, group IV versus group III), a protection comparable to that of the late phase of ischemic preconditioning (29+/-3%, P<0.01 group II versus group I). CONCLUSIONS: Direct gene transfer of the cDNA encoding membrane-bound Ec-SOD affords powerful cardioprotection, providing proof of principle for the effectiveness of antioxidant gene therapy against MI. |
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Authors:
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Q Li; R Bolli; Y Qiu; X L Tang; Y Guo; B A French |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Circulation Volume: 103 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2001 Apr |
Date Detail:
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Created Date: 2001-04-11 Completed Date: 2001-05-31 Revised Date: 2013-05-10 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1893-8 Citation Subset: IM |
Affiliation:
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Cardiology Research Laboratory, Division of Cardiology, University of Louisville and Jewish Hospital Heart and Lung Institute, Louisville, KY, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arrhythmias, Cardiac / etiology, physiopathology, prevention & control Blood Pressure / physiology COS Cells Consciousness Free Radical Scavengers / metabolism, therapeutic use Gene Expression Genetic Therapy* Heart Rate / physiology Heart Ventricles / pathology, physiopathology Humans Male Myocardial Infarction / genetics, pathology, therapy* Myocardial Reperfusion Injury / complications Organ Size RNA, Messenger / genetics, metabolism Rabbits Recombinant Fusion Proteins / genetics, metabolism, therapeutic use Superoxide Dismutase / genetics, metabolism*, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL043151/HL/NHLBI NIH HHS; R01 HL055757/HL/NHLBI NIH HHS; R01 HL058582/HL/NHLBI NIH HHS; R01HL-43151/HL/NHLBI NIH HHS; R01HL-55757/HL/NHLBI NIH HHS; R01HL-58582/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Free Radical Scavengers; 0/RNA, Messenger; 0/Recombinant Fusion Proteins; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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