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Diabetes 51:174-181, 2002
© 2002 by the American Diabetes Association, Inc.

Overexpression of Metallothionein Reduces Diabetic Cardiomyopathy

Qiangrong Liang1, Edward C. Carlson2, Rajakumar V. Donthi3, Patrica M. Kralik3, Xia Shen3, and Paul N. Epstein3

1 Division of Molecular Cardiovascular Biology, University of Cincinnati, Ohio
2 Department of Anatomy and Cell Biology, University of North Dakota, Grand Forks, North Dakota
3 Department of Pediatrics, University of Louisville, Louisville, Kentucky

Many diabetic patients suffer from cardiomyopathy, even in the absence of vascular disease. This diabetic cardiomyopathy predisposes patients to heart failure and mortality from myocardial infarction. Evidence from animal models suggests that reactive oxygen species play an important role in the development of diabetic cardiomyopathy. Our laboratory previously developed a transgenic mouse model with targeted overexpression of the antioxidant protein metallothionein (MT) in the heart. In this study we used MT-transgenic mice to test whether an antioxidant protein can reduce cardiomyopathy in the OVE26 transgenic model of diabetes. OVE26 diabetic mice exhibited cardiomyopathy characterized by significantly altered mRNA expression, clear morphological abnormalities, and reduced contractility under ischemic conditions. Diabetic hearts appeared to be under oxidative stress because they had significantly elevated oxidized glutathione (GSSG). Diabetic mice with elevated cardiac MT (called OVE26MT mice) were obtained by crossing OVE26 transgenic mice with MT transgenic mice. Hyperglycemia in OVE26MT mice was indistinguishable from hyperglycemia in OVE26 mice. Despite this, the MT transgene significantly reduced cardiomyopathy in diabetic mice: OVE26MT hearts showed more normal levels of mRNA and GSSG. Typically, OVE26MT hearts were found to be morphologically normal, and elevated MT improved the impaired ischemic contractility seen in diabetic hearts. These results demonstrate that cardiomyocyte-specific expression of an antioxidant protein reduces damage to the diabetic heart.


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Copyright © 2002 by the American Diabetes Association.