For therapeutic applications of ACE2 using transgenic overexpression of ACE2 in the hearts, the phenotypes are controversial; one study showed that cardiac overexpression of ACE2 protects the heart from ischemia-induced heart failure (Der Sarkissian et al., 2008) , whereas in the others overexpression of ACE2 was not beneficial, leading to fatal arrhythmia and severe fibrosis (Donoghue et al., 2003; Masson et al., 2009) .