AKT1 and cardiac hypertrophy: In contrast, cardioprotective effects of PDE-5 inhibitors have been evident through many other 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].