Recent studies reported that reduced expressions of APN in the plasma and pulmonary vasculature were observed in obesity-induced PH mice and circulating levels of APN show a negative correlation with the elevated RVSP [112,113], but more evidence shown that circulating levels of APN and/or lung APN expressions are higher in patients with PH (e.g., IPAH and CHD-PH) and rodents experimental PH models than their controls [[114], [115], [116], [117]]. This evidence concerns the gene ANPEP and obesity due to melanocortin 4 receptor deficiency.