Interestingly, PDE-5 inhibitors have been revealed to exert their protective effects through many signaling pathways, which are also common causative factors of T4-induced cardiac hypertrophy/dysfunction, such as oxidative stress, cardiomyocyte apoptosis, PI3K/Akt and ERK 1⁄2 [16, 17, 20, 31–34]. The gene discussed is AKT1; the disease is cardiac hypertrophy.