Hypoxia‐inducible Factor 1α is Critically Involved in Metallothionein Protection against Diabetic Cardiomyopathy

Abstract

The purpose of this study was to examine whether or not MT affects HIF‐1α activity in the heart of diabetic mice and in the cardiac cells leading to the regulation of angiogenic factors and glycolytic enzymes. Diabetes decreased cardiac VEGF and HK‐II protein level in mice; both cardiac‐specific MT and HIF‐1α over‐expression could relieve this suppression. Further analysis showed that MT over‐expression increased HIF‐1α protein level in diabetic heart. MT rescues HIF‐1α transcriptional activity leading to normalization of VEGF and HK‐II in cardiomyocytes under diabetic conditions. (Supported in part by an American Diabetes Association Grant 07‐07‐JF‐23)