Increased levels of cardiac ROS have been implicated in mitochondrial damage in heart failure.192,193 MAPK activation, cardiac hypertrophy, and fibrosis have also been linked to angiotensin II-induced mitochondrial ROS in HFrEF mice.194 In a mouse model of hypertensive cardiomyopathy induced by angiotensin II infusion,195 mitochondria-targeted antioxidant (N-acetyl cysteine) treatment, but not non-targeted ROS scavenging, mitigated cardiomyopathy. This evidence concerns the gene AGT and cardiomyopathy.