In cardiac-specific human NADPH oxidase 4 (Nox4) transgenic mice, an increase in NOX4 protein expression leads to an increase in ROS generation with cardiac interstitial fibrosis through activation of protein kinase B-mechanistic target of rapamycin (Akt-mTOR) and NF-κB signaling pathways (Zhao et al. 2015). Here, NOX4 is linked to Interstitial cardiac fibrosis.