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Since leptin (Ob) and its main receptor ObR-b contribute to systemic vascular cell proliferation and inflammation, we questioned whether targeting Ob\/ObR-b axis would be an effective antiproliferative and anti-inflammatory strategy against PAH.<\/jats:p><jats:p>In idiopathic PAH (iPAH), using human lung tissues and primary cell cultures (early passages \u22645), we demonstrate that pulmonary endothelial cells (P-ECs) over produce Ob and that PA-SMCs overexpress ObR-b. Furthermore, we obtain evidence that Ob enhances proliferation of human PA-SMCs<jats:italic>in vitro<\/jats:italic>and increases right ventricular systolic pressure in Ob-treated mice in the chronic hypoxia-induced pulmonary hypertension (PH) model. Using human cells, we also show that Ob leads to monocyte activation and increases cell adhesion molecule expression levels in P-ECs. We also find that Ob\/ObR-b axis contributes to PH susceptibility by using ObR-deficient rats, which display less severe hypoxia-induced PH (pulmonary haemodynamics, arterial muscularisation, PA-SMC proliferation and perivascular inflammation). Importantly, we demonstrate the efficacy of two curative strategies using a soluble Ob neutraliser and dichloroacetate in hypoxia-induced PH.<\/jats:p><jats:p>We demonstrate here that Ob\/ObR-b axis may represent anti-proliferative and anti-inflammatory targets in PAH.<\/jats:p>","DOI":"10.1183\/09031936.00193014","type":"journal-article","created":{"date-parts":[[2015,3,6]],"date-time":"2015-03-06T02:42:56Z","timestamp":1425609776000},"page":"1066-1080","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":75,"title":["Leptin signalling system as a target for pulmonary arterial hypertension 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