Others have also reported that PGC-1α downregulation does not uniformly present in human heart failure of other etiologies.29 Thus, our studies indicate that further activation of PGC-1α may not be beneficial in chagasic cardiomyopathy and may actually cause harm, as is noted in mice in whom overexpression of PGC-α resulted in tremendous mitochondrial biogenesis, leading to cardiomyopathy.25,30. This evidence concerns the gene PPARGC1A and cardiomyopathy.