ApoE−/−/LDL receptor (LDLr)−/− mice show increased NOX4 in aortic lesions and NOX4 knockdown, with short interfering (si)RNA in the aortic SMCs of these mice decreases H2O2, suggesting a role for NOX4-derived cellular ROS in atherosclerosis [20]. The gene discussed is APOE; the disease is atherosclerosis.