showed that a six-week treatment of macitentan was sufficient to reduce aortic lesion development in ApoE−/− mice after 17 weeks of a traditional Western diet.42 However, it must be noted that there is a far greater atherosclerotic lesion burden in ApoE−/− mice fed a Paigen diet when compared with ApoE−/− mice fed a traditional Western diet.15 Taken together, these data suggest either increasing the length of treatment or commencing treatment at an earlier stage in atherogenesis may reduce lesion burden or dampen the progression of atherosclerosis in our model. This evidence concerns the gene APOE and atherosclerosis.