Macitentan reverses pulmonary vascular remodeling associated with the PAH phenotype in HFD-fed ApoE−/− mice. Histologic and immunohistochemistry analysis of serial lung tissue sections revealed significant pulmonary vasculopathy consistent with a PAH phenotype in HFD-fed ApoE−/− mice. The gene discussed is APOE; the disease is pulmonary arterial hypertension.