High-fat diet (HFD)-fed ApoE−/− mice treated with an NOX2 inhibitor show reduced O2•− in aortic lesions [14], NOX2−/− mice are protected from injury-induced neointima formation [15] and show poor platelet adhesion to injured arteries [41], double ApoE−/−/NOX2−/− mice show reduced aortic O2•− levels and atherosclerosis [11] (Table 1). The gene discussed is APOE; the disease is atherosclerosis.