In stressed heart, ACE is up-regulated inversely to ACE2, leading to an imbalance in the ACE/ACE2 ratio, increased production of Ang II, and disturbance in RAAS homeostasis, which promote Ang II-induced hypertension, cardiac hypertrophy, and fibrosis (Wang et al., 2015a; Yang et al., 2016). Here, ACE is linked to cardiac hypertrophy.