APLN and pulmonary arterial hypertension: It greatly enhances the spatiotemporal signaling potential through the apelin receptor and how it is modulated in disease, with evidence that ELA, like apelin, is downregulated in human pulmonary arterial hypertension and animal models of the disease already demonstrated (Goetze et al., 2006; Alastalo et al., 2011; Chandra et al., 2011; Kim et al., 2013; Yang et al., 2017b).