{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:36:23Z","timestamp":1790516183314,"version":"4.1.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"am","delay-in-days":315,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100007150","name":"United Therapeutics Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007150","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","plefa.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Prostaglandins, Leukotrienes and Essential Fatty Acids"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1016\/j.plefa.2020.102158","type":"journal-article","created":{"date-parts":[[2020,7,5]],"date-time":"2020-07-05T10:23:54Z","timestamp":1593944634000},"page":"102158","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Downregulation of PGI2 pathway in Pulmonary Hypertension Group-III patients"],"prefix":"10.1016","volume":"160","author":[{"given":"Gulsev","family":"Ozen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Amgoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Abdelazeem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Mani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chabha","family":"Benyahia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel","family":"Bouhadoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexy","family":"Tran-Dinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Castier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Guyard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Longrois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Silverstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Norel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.plefa.2020.102158_bib0001","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000097754","article-title":"Mechanisms controlling vascular tone in pulmonary arterial hypertension: implications for vasodilator therapy","volume":"79","author":"Cogolludo","year":"2007","journal-title":"Pharmacology"},{"key":"10.1016\/j.plefa.2020.102158_bib0002","doi-asserted-by":"crossref","unstructured":"G. Simonneau, D. Montani, D.S. Celermajer, C.P. Denton, M.A. Gatzoulis, M. Krowka, P.G. Williams, R. Souza, Haemodynamic definitions and updated clinical classification of pulmonary hypertension, Eur. Respir. J., 53 (2019).","DOI":"10.1183\/13993003.01913-2018"},{"key":"10.1016\/j.plefa.2020.102158_bib0003","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1183\/13993003.01032-2015","volume":"46","author":"Galie","year":"2015","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.plefa.2020.102158_bib0004","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1056\/NEJM199507273330403","article-title":"Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension","volume":"333","author":"Giaid","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0005","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1161\/01.CIR.88.5.2117","article-title":"Thromboxane A2 and prostacyclin biosynthesis in children and adolescents with pulmonary vascular disease","volume":"88","author":"Adatia","year":"1993","journal-title":"Circulation"},{"key":"10.1016\/j.plefa.2020.102158_bib0006","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1056\/NEJM199207093270202","article-title":"An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension","volume":"327","author":"Christman","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0007","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1161\/01.CIR.84.6.2280","article-title":"Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation","volume":"84","author":"Yoshibayashi","year":"1991","journal-title":"Circulation"},{"key":"10.1016\/j.plefa.2020.102158_bib0008","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/pr.2014.209","article-title":"Altered prostanoid metabolism contributes to impaired angiogenesis in persistent pulmonary hypertension in a fetal lamb model","volume":"77","author":"Mahajan","year":"2015","journal-title":"Pediatr. Res."},{"key":"10.1016\/j.plefa.2020.102158_bib0009","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1164\/ajrccm.159.6.9804054","article-title":"Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension","volume":"159","author":"Tuder","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0010","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1046\/j.1440-1843.2003.00491.x","article-title":"Effects of IL-1beta, TNF-alpha, and macrophage migration inhibitory factor on prostacyclin synthesis in rat pulmonary artery smooth muscle cells","volume":"8","author":"Itoh","year":"2003","journal-title":"Respirology"},{"key":"10.1016\/j.plefa.2020.102158_bib0011","doi-asserted-by":"crossref","first-page":"e56058","DOI":"10.1371\/journal.pone.0056058","article-title":"Characterising the mechanism of airway smooth muscle beta2 adrenoceptor desensitization by rhinovirus infected bronchial epithelial cells","volume":"8","author":"Van Ly","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.plefa.2020.102158_bib0012","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbalip.2006.09.015","article-title":"Double-label expression studies of prostacyclin synthase, thromboxane synthase and COX isoforms in normal aortic endothelium","volume":"1771","author":"Kawka","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.plefa.2020.102158_bib0013","doi-asserted-by":"crossref","first-page":"H1005","DOI":"10.1152\/ajpheart.2001.281.3.H1005","article-title":"Effects of chronic estrogen-receptor blockade on ovine perinatal pulmonary circulation","volume":"281","author":"Parker","year":"2001","journal-title":"Am. J. Physiol. Heart Circ Physiol."},{"key":"10.1016\/j.plefa.2020.102158_bib0014","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1111\/j.1476-5381.2011.01276.x","article-title":"Endothelium-mediated control of vascular tone: COX-1 and COX-2 products","volume":"164","author":"Feletou","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.plefa.2020.102158_bib0015","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.prostaglandins.2015.04.007","article-title":"The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: role of membrane versus nuclear receptors","volume":"120","author":"Clapp","year":"2015","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"10.1016\/j.plefa.2020.102158_bib0016","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/sj.bjp.0705843","article-title":"Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone","volume":"142","author":"Norel","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.plefa.2020.102158_bib0017","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2147\/TCRM.S75122","article-title":"Prostanoid therapies in the management of pulmonary arterial hypertension","volume":"11","author":"LeVarge","year":"2015","journal-title":"Ther. Clin. Risk Manag."},{"key":"10.1016\/j.plefa.2020.102158_bib0018","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrcardio.2017.84","article-title":"Epidemiology and treatment of pulmonary arterial hypertension","volume":"14","author":"Lau","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.plefa.2020.102158_bib0019","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1164\/ajrccm.165.6.2106079","article-title":"Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial","volume":"165","author":"Simonneau","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0020","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ijcard.2018.08.043","article-title":"Pulmonary hypertension due to lung diseases: updated recommendations from the Cologne Consensus Conference 2018","volume":"272S","author":"Olschewski","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"10.1016\/j.plefa.2020.102158_bib0021","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1165\/ajrcmb\/1.6.489","article-title":"Decreased arterial wall prostaglandin production in neonatal calves with severe chronic pulmonary hypertension","volume":"1","author":"Badesch","year":"1989","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.plefa.2020.102158_bib0022","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0008-6363(02)00318-8","article-title":"Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension","volume":"55","author":"Blumberg","year":"2002","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.plefa.2020.102158_bib0023","doi-asserted-by":"crossref","first-page":"L475","DOI":"10.1152\/ajplung.2001.281.2.L475","article-title":"2nd, eNOS and prostanoid enzymes in lungs of newborn piglets with chronic aortopulmonary shunts","volume":"281","author":"Fike","year":"2001","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.plefa.2020.102158_bib0024","doi-asserted-by":"crossref","first-page":"L316","DOI":"10.1152\/ajplung.00228.2002","article-title":"Arachidonic acid metabolites and an early stage of pulmonary hypertension in chronically hypoxic newborn pigs","volume":"284","author":"Fike","year":"2003","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.plefa.2020.102158_bib0025","doi-asserted-by":"crossref","first-page":"e79215","DOI":"10.1371\/journal.pone.0079215","article-title":"Paracrine effects of bone marrow-derived endothelial progenitor cells: cyclooxygenase-2\/prostacyclin pathway in pulmonary arterial hypertension","volume":"8","author":"Jiang","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.plefa.2020.102158_bib0026","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1080\/00365510701673375","article-title":"Effects of selective and unselective endothelin-receptor antagonists on prostacyclin synthase gene expression in experimental pulmonary hypertension","volume":"68","author":"Schroll","year":"2008","journal-title":"Scand. J. Clin. Lab. Invest."},{"key":"10.1016\/j.plefa.2020.102158_bib0027","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1164\/rccm.201309-1697OC","article-title":"Functional prostacyclin synthase promoter polymorphisms. Impact in pulmonary arterial hypertension","volume":"189","author":"Stearman","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0028","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1742-1241.2011.02710.x","article-title":"Rodent models of pulmonary hypertension: harmonisation with the world health organisation\u2019s categorisation of human PH","author":"Ryan","year":"2011","journal-title":"Int. J. Clin. Pract. Suppl."},{"key":"10.1016\/j.plefa.2020.102158_bib0029","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCOUTCOMES.117.003973","article-title":"Increasing incidence and prevalence of world health organization groups 1 to 4 pulmonary hypertension: a population-based cohort study in Ontario, Canada","volume":"11","author":"Wijeratne","year":"2018","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"10.1016\/j.plefa.2020.102158_bib0030","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.1111\/bph.13939","article-title":"Inhibition of microsomal PGE synthase-1 reduces human vascular tone by increasing PGI2\u202f: a safer alternative to COX-2 inhibition","volume":"174","author":"Ozen","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.plefa.2020.102158_bib0031","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/bph.14854","article-title":"Bronchodilation induced by PGE2 is impaired in Group III pulmonary hypertension","volume":"177","author":"Ozen","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.plefa.2020.102158_bib0032","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1172\/JCI5911","article-title":"Pulmonary prostacyclin synthase overexpression in transgenic mice protects against development of hypoxic pulmonary hypertension","volume":"103","author":"Geraci","year":"1999","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.plefa.2020.102158_bib0033","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1161\/01.CIR.102.16.2005","article-title":"Gene transfer of human prostacyclin synthase ameliorates monocrotaline-induced pulmonary hypertension in rats","volume":"102","author":"Nagaya","year":"2000","journal-title":"Circulation"},{"key":"10.1016\/j.plefa.2020.102158_bib0034","first-page":"91","article-title":"Changes of thromboxane A2 (TXA2) and prostacyclin (PGI2) in COPD patients with pulmonary hypertension]","volume":"30","author":"Zheng","year":"1991","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"10.1016\/j.plefa.2020.102158_bib0035","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1161\/01.CIR.90.6.2952","article-title":"Plasma thromboxane B2 concentration in pulmonary hypertension associated with congenital heart disease","volume":"90","author":"Fuse","year":"1994","journal-title":"Circulation"},{"key":"10.1016\/j.plefa.2020.102158_bib0036","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1164\/rccm.200710-1519OC","article-title":"Role of the prostanoid EP4 receptor in iloprost-mediated vasodilatation in pulmonary hypertension","volume":"178","author":"Lai","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0037","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.3389\/fphar.2018.01518","article-title":"Mechanism of beraprost effects on pulmonary hypertension: contribution of cross-binding to PGE2 receptor 4 and modulation of O2 sensitive voltage-gated K(+) channels","volume":"9","author":"Fan","year":"2018","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.plefa.2020.102158_bib0038","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1164\/rccm.201001-0011OC","article-title":"Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension","volume":"182","author":"Falcetti","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0039","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1159\/000242498","article-title":"Iloprost improves gas exchange and exercise tolerance in patients with pulmonary hypertension and chronic obstructive pulmonary disease","volume":"79","author":"Dernaika","year":"2010","journal-title":"Respiration"},{"key":"10.1016\/j.plefa.2020.102158_bib0040","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00408-017-0081-7","article-title":"Inhaled treprostinil in pulmonary hypertension associated with lung disease","volume":"196","author":"Faria-Urbina","year":"2018","journal-title":"Lung"},{"key":"10.1016\/j.plefa.2020.102158_bib0041","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1378\/chest.08-1515","article-title":"Sustained improvement with iloprost in a COPD patient with severe pulmonary hypertension","volume":"135","author":"Hegewald","year":"2009","journal-title":"Chest"},{"key":"10.1016\/j.plefa.2020.102158_bib0042","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.rmed.2006.05.019","article-title":"Effects of nebulised iloprost on pulmonary function and gas exchange in severe pulmonary hypertension","volume":"101","author":"Reichenberger","year":"2007","journal-title":"Respir. Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0043","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1164\/ajrccm.160.2.9810008","article-title":"Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis","volume":"160","author":"Olschewski","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.plefa.2020.102158_bib0044","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.2147\/COPD.S141798","article-title":"Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension","volume":"12","author":"Wang","year":"2017","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"10.1016\/j.plefa.2020.102158_bib0045","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.chest.2017.06.008","article-title":"Pulmonary hypertension in parenchymal lung diseases: any future for new therapies?","volume":"153","author":"Harari","year":"2018","journal-title":"Chest"}],"container-title":["Prostaglandins, Leukotrienes and Essential Fatty Acids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0952327820301162?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0952327820301162?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T08:08:29Z","timestamp":1760602109000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0952327820301162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":45,"alternative-id":["S0952327820301162"],"URL":"https:\/\/doi.org\/10.1016\/j.plefa.2020.102158","relation":{},"ISSN":["0952-3278"],"issn-type":[{"value":"0952-3278","type":"print"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Downregulation of PGI2 pathway in Pulmonary Hypertension Group-III patients","name":"articletitle","label":"Article Title"},{"value":"Prostaglandins, Leukotrienes and Essential Fatty Acids","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.plefa.2020.102158","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"102158"}}