APLN and pulmonary arterial hypertension: Apelin peptide (but not the target receptor) is significantly reduced in cardiovascular disease such as heart failure and pulmonary arterial hypertension (PAH) (Goetze et al., 2006; Alastalo et al., 2011; Chandra et al., 2011; Yang et al., 2017b), where the therapeutic hypothesis is that apelin receptor agonists are needed to replace the missing endogenous peptide.