Protecting the heart through delivering DNA encoding for heme oxygenase-1 into skeletal muscle.
OBJECTIVE
To evaluate if remote gene delivery of HMOX-1 prior to myocardial infarction can prevent cardiac remodeling and preserve function, without causing general angiogenesis.


METHODS
Right quadriceps muscles of mice were treated with DNA encoding for HMOX-1 or empty vector (pcDNA) and electroporated to enhance nuclear uptake, while a third group received saline. Transfection efficacy was evaluated by real time PCR and situ hybridization in transfected muscle, contralateral muscle, and heart. Seven days after transfection baseline echocardiography was performed. Myocardial infarction was induced by ligation of the left coronary artery. Six weeks later heart function was reassessed by echocardiography. Hearts were extracted for evaluation of infarct size. Immunoflorescent staining was used to evaluate angiogenesis using the endothelial marker CD31 in cross-sections of the transfected quadriceps muscle, the untreated muscle, and hearts.


RESULTS
Gene delivery of HMOX-1 leads to a local expression of HMOX-1 in the treated muscle, but not in any other organ. HMOX-1 treated mice had reduced infarct size (p=0.03) and improved function evident as higher ejection fraction (p=0.001), improved fractional shortening (p<0.0001) and higher stroke volume (p=0.002). HMOX-1 did not cause angiogenesis in the heart or skeletal muscle.


CONCLUSIONS
Remote delivery of DNA encoding for HMOX-1 was cardioprotective, as evidenced by preserved cardiac structure and function. Angiogenesis was not induced by HMOX-1 treatment.
Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
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D
Bilbija
J A
JA
Gravning
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F
Haugen
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H
Attramadal
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Valen
D000818:Animals; D003331:Coronary Vessels / Q000254:growth & development; D004247:DNA / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D004452:Echocardiography; D018274:Electroporation; D015316:Genetic Therapy; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D014162:Transfection; D020257:Ventricular Remodeling
D004247:DNA; D051547:Heme Oxygenase-1