Myocardial protection with endogenous overexpression of manganese superoxide dismutase.

Abstract

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.

• Authors: K Suzuki, Y Sawa, H Ichikawa, Y Kaneda, H Matsuda
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 68 Issue 4 Pg. 1266-71 (Oct 1999) ISSN: 0003-4975 [Print] Netherlands
• PMID: 10543491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liposomes
• Recombinant Proteins
• Superoxide Dismutase
• Creatine Kinase

Topics

• Animals
• Creatine Kinase (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Gene Expression Regulation, Enzymologic (physiology)
• Gene Transfer Techniques
• Liposomes
• Myocardial Reperfusion Injury (enzymology, therapy)
• Rats
• Recombinant Proteins (administration & dosage)
• Respirovirus (genetics)
• Superoxide Dismutase (administration & dosage, genetics)
• Transfection (genetics)