ESR2 and pulmonary arterial hypertension: Down-regulation of ERβ has previously been observed in the lung and right heart in a right heart failure rat model.30 It has previously been shown that loss of ERβ in female mice leads to abnormal lung structures and systemic hypoxia contributing to ventricular hypertrophy.31 ERβ is likely therefore to be protective in experimental PH as previously described in male rodent models.32,33 The reduced expression of ERβ we observe in female human PASMCs from PAH patients and in the female SERT+ model of PH may result in a loss of the protective effects of oestrogen.