However, after transverse aortic constriction (TAC), Nrf2 (-/-) mice developed pathological cardiac hypertrophy, severe myocardial fibrosis and apoptosis, overt heart failure, and increased mortality, which was associated with increased myocardial levels of 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, coupled with the complete inhibition of several antioxidant genes in the myocardial tissue [60]. This evidence concerns the gene NFE2L2 and cardiac hypertrophy.