Myocardial protection with endogenous overexpression of manganese superoxide dismutase.
BACKGROUND
Superoxide dismutase (SOD) is a potent candidate for myocardial protection against ischemia-reperfusion injury; however, its clinical significance by means of exogenous administration remains controversial.


METHODS
To determine a role of endogenously overexpressed manganese SOD (Mn-SOD) in myocardial tolerance, rat hearts were transfected with Mn-SOD gene (group M) or no gene (group C) through intracoronary infusion of hemagglutinating virus of Japan (HVJ) liposome. Each group was divided into two subgroups to be subjected to ischemia-reperfusion using Langendorff apparatus with (subgroups M+ and C+) or without (M- and C-) administration of recombinant SOD.


RESULTS
Mn-SOD overexpression was confirmed in M with ELISA, activity measurement, and immunohistochemistry. The highest recoveries of maximum and minimum dp/dt and the least creatine phosphokinase (CPK) leakage were observed in M+. These recoveries were higher in M- than in C- and C+.


CONCLUSIONS
Thus, endogenous overexpression of Mn-SOD improved myocardial tolerance and its protective effect was enhanced by exogenous administration of SOD. These results suggest a possible strategy for myocardial protection with SOD: a combination of endogenous introduction through gene transfer with exogenous administration.
Suzuki
K
K
First Department of Surgery and Institute for Cellular and Molecular Biology, Osaka University, Japan.
Sawa
Y
Y
Ichikawa
H
H
Kaneda
Y
Y
Matsuda
H
H
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D018014:Gene Transfer Techniques; D008081:Liposomes; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000628:therapy; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage; D018108:Respirovirus / Q000235:genetics; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000235:genetics*; D014162:Transfection / Q000235:genetics
D008081:Liposomes; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D003402:Creatine Kinase