Macitentan improves cardiac hemodynamics associated with PAH phenotype in HFD-fed ApoE−/− mice. HFD-fed ApoE−/− mice developed a PAH phenotype similar to that previously described16,36 as assessed by a decrease in pulmonary artery acceleration time (PA-AT; Fig. 1a), increase in RV systolic pressure (RVSP; Fig. 1b), and changes in RV function (Fig. 1c, d). The gene discussed is APOE; the disease is pulmonary arterial hypertension.