In addition, NOX4 can promote volume overload via inactivation of protein phosphatase 2A(PP2A) and further increase Akt phosphorylation and modulation of RPS6 and 4E-BP1 downstream proteins, whereas NOX4−/− mice demonstrated less eccentric LV remodeling and attenuated cardiac hypertrophy due to reduction in phosphorylated Akt levels [31]. This evidence concerns the gene NOX4 and cardiac hypertrophy.