{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T17:31:56Z","timestamp":1772645516519,"version":"3.50.1"},"reference-count":58,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,8,6]],"date-time":"2017-08-06T00:00:00Z","timestamp":1501977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.fr","clinicalkey.com.au","pediatr-neonatol.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pediatrics &amp; Neonatology"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1016\/j.pedneo.2016.12.008","type":"journal-article","created":{"date-parts":[[2017,8,12]],"date-time":"2017-08-12T10:16:35Z","timestamp":1502532995000},"page":"112-119","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pulmonary artery hypertension in childhood: The transforming growth factor-\u03b2 superfamily-related genes"],"prefix":"10.1016","volume":"59","author":[{"given":"Shi-Min","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.pedneo.2016.12.008_bib1","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1161\/CIR.0000000000000329","article-title":"Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society","volume":"132","author":"Abman","year":"2015","journal-title":"Circulation"},{"key":"10.1016\/j.pedneo.2016.12.008_bib2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/01.crd.0000249381.49138.b9","article-title":"Pulmonary artery hypertension: caveolin-1 and eNOS interrelationship: a new perspective","volume":"15","author":"Mathew","year":"2007","journal-title":"Cardiol Rev"},{"key":"10.1016\/j.pedneo.2016.12.008_bib3","first-page":"195","article-title":"Recent studies in primary pulmonary hypertension,including pharmacodynamic observations on pulmonary vascular resistance","volume":"30","author":"Dresdale","year":"1954","journal-title":"Bull N Y Acad Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib4","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1136\/jmg.37.10.741","article-title":"Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-\u03b2 family","volume":"37","author":"Thomson","year":"2000","journal-title":"J Med Genet"},{"key":"10.1016\/j.pedneo.2016.12.008_bib5","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1161\/01.RES.0000243584.45145.3f","article-title":"Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms","volume":"99","author":"Stenmark","year":"2006","journal-title":"Circ Res"},{"key":"10.1016\/j.pedneo.2016.12.008_bib6","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1161\/CIRCULATIONAHA.105.601930","article-title":"Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension","volume":"113","author":"Elliott","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.pedneo.2016.12.008_bib7","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1164\/rccm.200712-1807OC","article-title":"Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation","volume":"177","author":"Sztrymf","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib8","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMoa1211097","article-title":"A novel channelopathy in pulmonary arterial hypertension","volume":"369","author":"Ma","year":"2013","journal-title":"N Engl J Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib9","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","article-title":"Mechanisms of TGF-\u03b2 signaling from cell membrane to the nucleus","volume":"113","author":"Shi","year":"2003","journal-title":"Cell"},{"key":"10.1016\/j.pedneo.2016.12.008_bib10","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1161\/01.CIR.0000153798.78540.87","article-title":"Transforming growth factor-\u03b2 receptor mutations and pulmonary arterial hypertension in childhood","volume":"111","author":"Harrison","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.pedneo.2016.12.008_bib11","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1253\/circj.72.127","article-title":"Implications of mutations of activin receptor-like kinase 1 gene (ALK1) in addition to bone morphogenetic protein receptor II gene (BMPR2) in children with pulmonary arterial hypertension","volume":"72","author":"Fujiwara","year":"2008","journal-title":"Circ J"},{"key":"10.1016\/j.pedneo.2016.12.008_bib12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s00439-004-1196-5","article-title":"Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients","volume":"116","author":"Letteboer","year":"2005","journal-title":"Hum Genet"},{"key":"10.1016\/j.pedneo.2016.12.008_bib13","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1159\/000098818","article-title":"Genes and pulmonary arterial hypertension","volume":"74","author":"Sztrymf","year":"2007","journal-title":"Respiration"},{"key":"10.1016\/j.pedneo.2016.12.008_bib14","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1164\/rccm.201106-1130OC","article-title":"Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8","volume":"184","author":"Drake","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib15","unstructured":"Hereditary pulmonary arterial hypertension and BMPR2. Available at: http:\/\/www.arup.utah.edu\/database\/BMPR2\/BMPR2_welcome.php Accessed May 18, 2016."},{"key":"10.1016\/j.pedneo.2016.12.008_bib16","doi-asserted-by":"crossref","first-page":"278","DOI":"10.7326\/0003-4819-148-4-200802190-00006","article-title":"Narrative review: the enigma of pulmonary arterial hypertension: new insights from genetic studies","volume":"148","author":"Newman","year":"2008","journal-title":"Ann Intern Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib17","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/CIRCULATIONAHA.108.847707","article-title":"Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies","volume":"121","author":"Archer","year":"2010","journal-title":"Circulation"},{"key":"10.1016\/j.pedneo.2016.12.008_bib18","doi-asserted-by":"crossref","first-page":"L861","DOI":"10.1152\/ajplung.00201.2010","article-title":"MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration","volume":"299","author":"Sarkar","year":"2010","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.pedneo.2016.12.008_bib19","doi-asserted-by":"crossref","first-page":"169069","DOI":"10.1155\/2015\/169069","article-title":"Modulation of miRNAs in pulmonary hypertension","volume":"2015","author":"Gupta","year":"2015","journal-title":"Int J Hypertens"},{"key":"10.1016\/j.pedneo.2016.12.008_bib20","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1136\/hrt.44.3.352","article-title":"Primary pulmonary hypertension: effects of nifedipine","volume":"44","author":"Camerini","year":"1980","journal-title":"Br Heart J"},{"key":"10.1016\/j.pedneo.2016.12.008_bib21","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1378\/chest.92.3.400","article-title":"Nifedipine in pulmonary arterial hypertension. Importance of Raynaud's phenomenon","volume":"92","author":"Fisher","year":"1987","journal-title":"Chest"},{"key":"10.1016\/j.pedneo.2016.12.008_bib22","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1136\/hrt.47.5.511","article-title":"Failure of nifedipine treatment in primary pulmonary hypertension","volume":"47","author":"Berkenboom","year":"1982","journal-title":"Br Heart J"},{"key":"10.1016\/j.pedneo.2016.12.008_bib23","doi-asserted-by":"crossref","first-page":"L872","DOI":"10.1152\/ajplung.00309.2006","article-title":"Overexpression of human bone morphogenetic protein receptor 2 does not ameliorate monocrotaline pulmonary arterial hypertension","volume":"292","author":"McMurtry","year":"2007","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.pedneo.2016.12.008_bib24","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1073\/pnas.97.6.2626","article-title":"Activin receptor-like kinase 1 modulates transforming growth factor-\u03b21 signaling in the regulation of angiogenesis","volume":"97","author":"Oh","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.pedneo.2016.12.008_bib25","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1056\/NEJM200108023450503","article-title":"Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia","volume":"345","author":"Trembath","year":"2001","journal-title":"N Engl J Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib26","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1164\/rccm.200908-1284OC","article-title":"Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation","volume":"181","author":"Girerd","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10456-008-9101-9","article-title":"Endoglin in angiogenesis and vascular diseases","volume":"11","author":"ten Dijke","year":"2008","journal-title":"Angiogenesis"},{"key":"10.1016\/j.pedneo.2016.12.008_bib28","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1172\/JCI33338","article-title":"Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration","volume":"119","author":"Zhao","year":"2009","journal-title":"J Clin Investig"},{"key":"10.1016\/j.pedneo.2016.12.008_bib29","doi-asserted-by":"crossref","first-page":"e100310","DOI":"10.1371\/journal.pone.0100310","article-title":"Key role of the endothelial TGF-\u03b2\/ALK1\/endoglin signaling pathway in humans and rodents pulmonary hypertension","volume":"9","author":"Gore","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.pedneo.2016.12.008_bib30","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1161\/01.RES.0000159936.38601.22","article-title":"A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia","volume":"96","author":"Toporsian","year":"2005","journal-title":"Circ Res"},{"key":"10.1016\/j.pedneo.2016.12.008_bib31","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1378\/chest.129.3.696","article-title":"Loss of caveolin and heme oxygenase expression in severe pulmonary hypertension","volume":"129","author":"Achcar","year":"2006","journal-title":"Chest"},{"key":"10.1016\/j.pedneo.2016.12.008_bib32","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P","article-title":"Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome)","volume":"91","author":"Shovlin","year":"2000","journal-title":"Am J Med Genet"},{"key":"10.1016\/j.pedneo.2016.12.008_bib33","doi-asserted-by":"crossref","first-page":"573432","DOI":"10.1155\/2011\/573432","article-title":"Cell-specific dual role of caveolin-1 in pulmonary hypertension","volume":"2011","author":"Mathew","year":"2011","journal-title":"Pulm Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib34","first-page":"173970","article-title":"Serum caveolin-1 as a novel biomarker in idiopathic pulmonary artery hypertension","volume":"2015","author":"Wang","year":"2015","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.pedneo.2016.12.008_bib35","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1161\/CIRCULATIONAHA.107.731679","article-title":"Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation: Ca2+ signals and gap junction function are regulated by caveolin in endothelial cells","volume":"117","author":"Saliez","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.pedneo.2016.12.008_bib36","doi-asserted-by":"crossref","first-page":"L523","DOI":"10.1152\/ajplung.00013.2006","article-title":"Role of caveolin-1 in p42\/p44 MAP kinase activation and proliferation of human airway smooth muscle","volume":"291","author":"Gosens","year":"2006","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.pedneo.2016.12.008_bib37","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1126\/science.1062688","article-title":"Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice","volume":"293","author":"Drab","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.pedneo.2016.12.008_bib38","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1096\/fj.06-7719com","article-title":"Mechanisms of cardiac protection from ischemia\/reperfusion injury: a role for caveolae and caveolin-1","volume":"21","author":"Patel","year":"2007","journal-title":"FASEB J"},{"key":"10.1016\/j.pedneo.2016.12.008_bib39","doi-asserted-by":"crossref","first-page":"7304","DOI":"10.1074\/jbc.270.13.7304","article-title":"Regulation of transforming growth factor-\u03b2 activation by discrete sequences of thrombospondin 1","volume":"270","author":"Schultz-Cherry","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/j.pedneo.2016.12.008_bib40","author":"Frantz"},{"key":"10.1016\/j.pedneo.2016.12.008_bib41","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3389\/fphys.2014.00134","article-title":"Regulation of soluble guanylate cyclase by matricellular thrombospondins: implications for blood flow","volume":"5","author":"Rogers","year":"2014","journal-title":"Front Physiol"},{"key":"10.1016\/j.pedneo.2016.12.008_bib42","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1586\/17476348.2014.909731","article-title":"KCNK3: new gene target for pulmonary hypertension?","volume":"8","author":"Girerd","year":"2014","journal-title":"Expert Rev Respir Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib43","doi-asserted-by":"crossref","first-page":"C1837","DOI":"10.1152\/ajpcell.00405.2006","article-title":"Function of Kv1.5 channels and genetic variations of KCNA5 in patients with idiopathic pulmonary arterial hypertension","volume":"292","author":"Remillard","year":"2007","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.pedneo.2016.12.008_bib44","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1479-5876-12-39","article-title":"Potential therapeutic targets for hypoxia-induced pulmonary artery hypertension","volume":"12","author":"Dong","year":"2014","journal-title":"J Transl Med"},{"key":"10.1016\/j.pedneo.2016.12.008_bib45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1465-9921-14-3","article-title":"Hemodynamic and genetic analysis in children with idiopathic, heritable, and congenital heart disease associated pulmonary arterial hypertension","volume":"14","author":"Pfarr","year":"2013","journal-title":"Respir Res"},{"key":"10.1016\/j.pedneo.2016.12.008_bib46","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1203\/01.PDR.0000139481.20847.D0","article-title":"Primary pulmonary hypertension in children may have a different genetic background than in adults","volume":"56","author":"Gr\u00fcnig","year":"2004","journal-title":"Pediatr Res"},{"key":"10.1016\/j.pedneo.2016.12.008_bib47","doi-asserted-by":"crossref","first-page":"e100261","DOI":"10.1371\/journal.pone.0100261","article-title":"Novel mutations in BMPR2, ACVRL1 and KCNA5 genes and hemodynamic parameters in patients with pulmonary arterial hypertension","volume":"9","author":"Pousada","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.pedneo.2016.12.008_bib48","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1253\/circj.CJ-11-1281","article-title":"Missense mutations of the BMPR1B (ALK6) gene in childhood idiopathic pulmonary arterial hypertension","volume":"76","author":"Chida","year":"2012","journal-title":"Circ J"},{"key":"10.1016\/j.pedneo.2016.12.008_bib49","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1183\/09031936.04.00018604","article-title":"BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease","volume":"24","author":"Roberts","year":"2004","journal-title":"Eur Respir J"},{"key":"10.1016\/j.pedneo.2016.12.008_bib50","unstructured":"Liu XG, Qiao F, Lu FL, Xu ZY. Changes of miR-19a and BMPR2 in lung tissue of CHD-PAH and its significance. http:\/\/dx.doi.org\/10.3877\/cma.j.issn.1674-0785.2013.22.043. [in Chinese]"},{"key":"10.1016\/j.pedneo.2016.12.008_bib51","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1136\/jmg.2008.062703","article-title":"A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension","volume":"46","author":"Shintani","year":"2009","journal-title":"J Med Genet"},{"key":"10.1016\/j.pedneo.2016.12.008_bib52","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1002\/humu.21605","article-title":"Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertension","volume":"32","author":"Nasim","year":"2011","journal-title":"Hum Mutat"},{"key":"10.1016\/j.pedneo.2016.12.008_bib53","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1161\/CIRCGENETICS.112.965335","article-title":"Novel inheritable caveolin-1 mutations in pulmonary arterial hypertension","volume":"5","author":"Desai","year":"2012","journal-title":"Circ Cardiovasc Genet"},{"issue":"1 Suppl. 1","key":"10.1016\/j.pedneo.2016.12.008_bib54","article-title":"Newly identified caveolin-1 mutation associated with heritable human pulmonary arterial hypertension mediates hyperproliferation via augmented calcium signaling (1089.10)","volume":"28","author":"Marsboom","year":"2014","journal-title":"FASEB J"},{"key":"10.1016\/j.pedneo.2016.12.008_bib55","doi-asserted-by":"crossref","first-page":"L541","DOI":"10.1152\/ajplung.00282.2011","article-title":"Loss-of-function thrombospondin-1 mutations in familial pulmonary hypertension","volume":"302","author":"Maloney","year":"2012","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"10.1016\/j.pedneo.2016.12.008_bib56","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1097\/MOP.0b013e3283464a52","article-title":"Recent progress in understanding pediatric pulmonary hypertension","volume":"23","author":"Abman","year":"2011","journal-title":"Curr Opin Pediatr"},{"key":"10.1016\/j.pedneo.2016.12.008_bib57","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1183\/09031936.00056110","article-title":"Pulmonary arterial hypertension: a comparison between children and adults","volume":"37","author":"Barst","year":"2011","journal-title":"Eur Respir J"},{"key":"10.1016\/j.pedneo.2016.12.008_bib58","doi-asserted-by":"crossref","first-page":"D117","DOI":"10.1016\/j.jacc.2013.10.028","article-title":"Pediatric pulmonary hypertension","volume":"62","author":"Ivy","year":"2013","journal-title":"J Am Coll Cardiol"}],"container-title":["Pediatrics &amp; Neonatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1875957217304862?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1875957217304862?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T11:25:35Z","timestamp":1535455535000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1875957217304862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["S1875957217304862"],"URL":"https:\/\/doi.org\/10.1016\/j.pedneo.2016.12.008","relation":{},"ISSN":["1875-9572"],"issn-type":[{"value":"1875-9572","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pulmonary artery hypertension in childhood: The transforming growth factor-\u03b2 superfamily-related genes","name":"articletitle","label":"Article Title"},{"value":"Pediatrics & Neonatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pedneo.2016.12.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Taiwan Pediatric Association. Published by Elsevier Taiwan LLC.","name":"copyright","label":"Copyright"}]}}