{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:08:40Z","timestamp":1791896920181,"version":"4.3.4"},"reference-count":106,"publisher":"European Respiratory Society (ERS)","issue":"146","content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir Rev"],"accepted":{"date-parts":[[2017,12,8]]},"published-print":{"date-parts":[[2017,12,31]]},"abstract":"<jats:p>The pathobiology of pulmonary arterial hypertension (PAH) is complex and incompletely understood. Although three pathogenic pathways have been relatively well characterised, it is widely accepted that dysfunction in a multitude of other cellular processes is likely to play a critical role in driving the development of PAH. Currently available therapies, which all target one of the three well-characterised pathways, provide significant benefits for patients; however, PAH remains a progressive and ultimately fatal disease. The development of drugs to target alternative pathogenic pathways is, therefore, an attractive proposition and one that may complement existing treatment regimens to improve outcomes for patients. Considerable research has been undertaken to identify the role of the less well-understood pathways and in this review we will highlight some of the key discoveries and the potential for utility as therapeutic targets.<\/jats:p>","DOI":"10.1183\/16000617.0093-2017","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T01:10:41Z","timestamp":1513818641000},"page":"170093","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":85,"title":["Pathobiology of pulmonary arterial hypertension: understanding the roads less travelled"],"prefix":"10.1183","volume":"26","author":[{"given":"Anna R.","family":"Hemnes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Humbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2017,12,20]]},"reference":[{"key":"2024102403314806000_26.146.170093.1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.006974"},{"key":"2024102403314806000_26.146.170093.2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq152"},{"key":"2024102403314806000_26.146.170093.3","unstructured":"Alberts B , Johnson A , Lewis J , et al. Molecular Biology of the Cell. 4th Edn. New York, Garland Science, 2002; p. 1616."},{"key":"2024102403314806000_26.146.170093.4","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00047.2013"},{"key":"2024102403314806000_26.146.170093.5","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1165\/rcmb.2015-0323TR","article-title":"Endothelial and smooth muscle cell interactions in the pathobiology of pulmonary hypertension","volume":"54","author":"Gao","year":"2016","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2024102403314806000_26.146.170093.6","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-1-61779-523-7_16","article-title":"Vascular smooth muscle cells: isolation, culture, and characterization","volume":"843","author":"Metz","year":"2012","journal-title":"Methods Mol Biol"},{"key":"2024102403314806000_26.146.170093.7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10741-015-9519-2","article-title":"Molecular pathogenesis and current pathology of pulmonary hypertension","volume":"21","author":"de Jesus Perez","year":"2016","journal-title":"Heart Fail Rev"},{"key":"2024102403314806000_26.146.170093.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.025"},{"key":"2024102403314806000_26.146.170093.9","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.celrep.2015.09.049","article-title":"Matrix remodeling promotes pulmonary hypertension through feedback mechanoactivation of the YAP\/TAZ-miR-130\/301 circuit","volume":"13","author":"Bertero","year":"2015","journal-title":"Cell Rep"},{"key":"2024102403314806000_26.146.170093.10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI86387"},{"key":"2024102403314806000_26.146.170093.11","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020617"},{"key":"2024102403314806000_26.146.170093.12","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.022479"},{"key":"2024102403314806000_26.146.170093.13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.008750"},{"key":"2024102403314806000_26.146.170093.14","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-007-9426-3"},{"key":"2024102403314806000_26.146.170093.15","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-009-9684-3"},{"key":"2024102403314806000_26.146.170093.16","doi-asserted-by":"publisher","DOI":"10.1007\/s12195-015-0386-7"},{"key":"2024102403314806000_26.146.170093.17","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006927"},{"key":"2024102403314806000_26.146.170093.18","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.234286"},{"key":"2024102403314806000_26.146.170093.19","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.007469"},{"key":"2024102403314806000_26.146.170093.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2014.01.011"},{"key":"2024102403314806000_26.146.170093.21","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/14728222.2017.1275567","article-title":"Restoring BMPRII functions in pulmonary arterial hypertension: opportunities, challenges and limitations","volume":"21","author":"Guignabert","year":"2017","journal-title":"Expert Opin Ther Targets"},{"key":"2024102403314806000_26.146.170093.22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.4103\/2045-8932.87293","article-title":"The genetics of pulmonary arterial hypertension in the post-BMPR2 era","volume":"1","author":"Fessel","year":"2011","journal-title":"Pulm Circ"},{"key":"2024102403314806000_26.146.170093.23","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000012754.72951.3D"},{"key":"2024102403314806000_26.146.170093.24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83361"},{"key":"2024102403314806000_26.146.170093.25","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201205-0886OC"},{"key":"2024102403314806000_26.146.170093.26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.492488"},{"key":"2024102403314806000_26.146.170093.27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14079"},{"key":"2024102403314806000_26.146.170093.28","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3695"},{"key":"2024102403314806000_26.146.170093.29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65592"},{"key":"2024102403314806000_26.146.170093.30","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.300483"},{"key":"2024102403314806000_26.146.170093.31","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3877"},{"key":"2024102403314806000_26.146.170093.32","doi-asserted-by":"publisher","DOI":"10.1086\/303059"},{"key":"2024102403314806000_26.146.170093.33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24838"},{"key":"2024102403314806000_26.146.170093.34","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1183\/09031936.98.11030554","article-title":"Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients","volume":"11","author":"Humbert","year":"1998","journal-title":"Eur Respir J"},{"key":"2024102403314806000_26.146.170093.35","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-1037OC"},{"key":"2024102403314806000_26.146.170093.36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35070"},{"key":"2024102403314806000_26.146.170093.37","doi-asserted-by":"publisher","DOI":"10.1378\/chest.126.4.1255"},{"key":"2024102403314806000_26.146.170093.38","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0317OC"},{"key":"2024102403314806000_26.146.170093.39","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000765"},{"key":"2024102403314806000_26.146.170093.40","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.001460"},{"key":"2024102403314806000_26.146.170093.41","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc051946"},{"key":"2024102403314806000_26.146.170093.42","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201001-0123OC"},{"key":"2024102403314806000_26.146.170093.43","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-145-2-200607180-00019"},{"key":"2024102403314806000_26.146.170093.44","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.064097"},{"key":"2024102403314806000_26.146.170093.45","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0084-2016"},{"key":"2024102403314806000_26.146.170093.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.006"},{"key":"2024102403314806000_26.146.170093.47","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00046612"},{"key":"2024102403314806000_26.146.170093.48","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.004555"},{"key":"2024102403314806000_26.146.170093.49","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s12016-011-8265-z","article-title":"The role of inflammation and autoimmunity in the pathophysiology of pulmonary arterial hypertension","volume":"44","author":"Kherbeck","year":"2013","journal-title":"Clin Rev Allerg Immunol"},{"key":"2024102403314806000_26.146.170093.50","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301141"},{"key":"2024102403314806000_26.146.170093.51","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201105-0927OC"},{"key":"2024102403314806000_26.146.170093.52","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.5.7735624"},{"key":"2024102403314806000_26.146.170093.53","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200610-1559OC"},{"key":"2024102403314806000_26.146.170093.54","doi-asserted-by":"publisher","DOI":"10.1378\/chest.100.5.1268"},{"key":"2024102403314806000_26.146.170093.55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005981"},{"key":"2024102403314806000_26.146.170093.56","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.3.1689"},{"key":"2024102403314806000_26.146.170093.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.04.007"},{"key":"2024102403314806000_26.146.170093.58","doi-asserted-by":"publisher","DOI":"10.1002\/art.23303"},{"key":"2024102403314806000_26.146.170093.59","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211097"},{"key":"2024102403314806000_26.146.170093.60","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/cge.12869","article-title":"An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension","volume":"91","author":"Navas Tejedor","year":"2017","journal-title":"Clin Genet"},{"key":"2024102403314806000_26.146.170093.61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb01172.x"},{"key":"2024102403314806000_26.146.170093.62","doi-asserted-by":"publisher","DOI":"10.1586\/17476348.2014.909731"},{"key":"2024102403314806000_26.146.170093.63","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201404136"},{"key":"2024102403314806000_26.146.170093.64","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020951"},{"key":"2024102403314806000_26.146.170093.65","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)78495-6"},{"key":"2024102403314806000_26.146.170093.66","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.609008"},{"key":"2024102403314806000_26.146.170093.67","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000062688.76508.B3"},{"key":"2024102403314806000_26.146.170093.68","doi-asserted-by":"publisher","DOI":"10.1086\/674312"},{"key":"2024102403314806000_26.146.170093.69","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000175878.32920.17"},{"key":"2024102403314806000_26.146.170093.70","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2006.05.007"},{"key":"2024102403314806000_26.146.170093.71","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00010409"},{"key":"2024102403314806000_26.146.170093.72","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.016133"},{"key":"2024102403314806000_26.146.170093.73","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1742-1241.2010.02523.x","article-title":"Metabolic and hormonal derangements in pulmonary hypertension: from mouse to man","volume":"268","author":"Pugh","year":"2010","journal-title":"Int J Clin Pract Suppl"},{"key":"2024102403314806000_26.146.170093.74","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201107-1293OC"},{"key":"2024102403314806000_26.146.170093.75","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0141"},{"key":"2024102403314806000_26.146.170093.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.02.057"},{"key":"2024102403314806000_26.146.170093.77","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00100510"},{"key":"2024102403314806000_26.146.170093.78","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2013.08.007"},{"key":"2024102403314806000_26.146.170093.79","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.160960"},{"key":"2024102403314806000_26.146.170093.80","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1404"},{"key":"2024102403314806000_26.146.170093.81","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305265"},{"key":"2024102403314806000_26.146.170093.82","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.006167"},{"key":"2024102403314806000_26.146.170093.83","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.963314"},{"key":"2024102403314806000_26.146.170093.84","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2021"},{"key":"2024102403314806000_26.146.170093.85","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.916098"},{"key":"2024102403314806000_26.146.170093.86","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0036-2016"},{"key":"2024102403314806000_26.146.170093.87","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0166TR"},{"key":"2024102403314806000_26.146.170093.88","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307004"},{"key":"2024102403314806000_26.146.170093.89","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201411-2128OC"},{"key":"2024102403314806000_26.146.170093.90","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2014-0045TR"},{"key":"2024102403314806000_26.146.170093.91","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0094-2017"},{"key":"2024102403314806000_26.146.170093.92","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/cphy.c100005","article-title":"Pulmonary vascular stiffness: measurement, modeling, and implications in normal and hypertensive pulmonary circulations","volume":"1","author":"Hunter","year":"2011","journal-title":"Compr Physiol"},{"key":"2024102403314806000_26.146.170093.93","doi-asserted-by":"crossref","first-page":"12422","DOI":"10.1038\/ncomms12422","article-title":"Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells","volume":"7","author":"Chen","year":"2016","journal-title":"Nat Commun"},{"key":"2024102403314806000_26.146.170093.94","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.236927"},{"key":"2024102403314806000_26.146.170093.95","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00337.2013"},{"key":"2024102403314806000_26.146.170093.96","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.004526"},{"key":"2024102403314806000_26.146.170093.97","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201203-0383OC"},{"key":"2024102403314806000_26.146.170093.98","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00101211"},{"key":"2024102403314806000_26.146.170093.99","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06-2913"},{"key":"2024102403314806000_26.146.170093.100","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200510-1668OC"},{"key":"2024102403314806000_26.146.170093.101","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00092306"},{"key":"2024102403314806000_26.146.170093.102","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1140"},{"key":"2024102403314806000_26.146.170093.103","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2009.05.016"},{"key":"2024102403314806000_26.146.170093.104","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2010.04.038"},{"key":"2024102403314806000_26.146.170093.105","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201302-0302OC"},{"key":"2024102403314806000_26.146.170093.106","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1152\/japplphysiol.00677.2004","article-title":"Insights by Peruvian scientists into the pathogenesis of human chronic hypoxic pulmonary hypertension","volume":"98","author":"Reeves","year":"2004","journal-title":"J Appl Physiol"}],"container-title":["European Respiratory Review"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/16000617.0093-2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T04:59:38Z","timestamp":1740373178000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/16000617.0093-2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,20]]},"references-count":106,"journal-issue":{"issue":"146","published-online":{"date-parts":[[2017,12,20]]},"published-print":{"date-parts":[[2017,12,31]]}},"alternative-id":["10.1183\/16000617.0093-2017"],"URL":"https:\/\/doi.org\/10.1183\/16000617.0093-2017","relation":{},"ISSN":["0905-9180","1600-0617"],"issn-type":[{"value":"0905-9180","type":"print"},{"value":"1600-0617","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,20]]}}}