Mice globally overexpressing human HO-1 were protected from DOX-induced dilated cardiomyopathy, cardiac cytoarchitectural derangement, and infiltration of mononuclear phagocytes. Cardiac-specific overexpression of HO-1 ameliorated DOX-mediated dilation of the sarcoplasmic reticulum as well as mitochondrial fragmentation and increased numbers of damaged mitochondria in autophagic vacuoles. This evidence concerns the gene HMOX1 and dilated cardiomyopathy.