{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:09:17Z","timestamp":1792843757144,"version":"4.5.0"},"reference-count":68,"publisher":"European Respiratory Society (ERS)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2013,5,24]]},"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:p>Pulmonary artery smooth muscle cells (PASMC), in pulmonary arterial hypertension (PAH), contribute to obliterative vascular remodelling and are characterised by enhanced proliferation, suppressed apoptosis and, a much less studied, increased migration potential. One of the major proteins that regulate cell migration is focal adhesion kinase (FAK), but its role in PAH is not fully understood. We hypothesised that targeting cell migration by FAK inhibition may be a new therapeutic strategy in PAH.<\/jats:p>\n                  <jats:p>\n                    <jats:italic>In vivo<\/jats:italic>\n                    , inhalation of FAK-siRNA (n=5) or oral delivery of PF-228 (FAK inhibitor PF-573 228; n=5) inhibited rat monocrotaline induced PAH, improving the haemodynamics, vascular remodelling (media thickness), and right ventricular hypertrophy.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , FAK was activated in PAH human lungs (n=8) or PASMC when compared to those form healthy subjects (Western blot, n=5), in a Src-dependent manner, as it was reversed by the specific Src inhibitor PP2. The degree of FAK phosphorylation at Y576 correlated positively with pulmonary vascular resistance in PAH patients. FAK inhibition (siRNA, PF-228 and PP2) in PAH-PASMCs induced a fivefold increase in apoptosis (percentage of terminal deoxynucleotidyl transferase dUTP nick end labelling), a 2.5-fold decrease in proliferation (%Ki67), an 18% decrease in cell migration (colorimetric assay) and a 50% decrease in cell invasion (wound healing).\n                  <\/jats:p>\n                  <jats:p>Suppressing PASMC migration by FAK inhibition inhibits PAH progression and may open a new therapeutic window in PAH.<\/jats:p>","DOI":"10.1183\/09031936.00181312","type":"journal-article","created":{"date-parts":[[2013,7,11]],"date-time":"2013-07-11T22:55:46Z","timestamp":1373583346000},"page":"531-544","source":"Crossref","is-referenced-by-count":62,"title":["Targeting cell motility in pulmonary arterial hypertension"],"prefix":"10.1183","volume":"43","author":[{"given":"Roxane","family":"Paulin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolyane","family":"Meloche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Courboulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alois","family":"Haromy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Courchesne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steeve","family":"Provencher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos D.","family":"Michelakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Bonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2013,7,11]]},"reference":[{"key":"2026092109352406000_43.2.531.1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23203"},{"key":"2026092109352406000_43.2.531.2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.114.3_Supplement.225S"},{"key":"2026092109352406000_43.2.531.3","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0788-5"},{"key":"2026092109352406000_43.2.531.4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00284.2002"},{"key":"2026092109352406000_43.2.531.5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102750200"},{"key":"2026092109352406000_43.2.531.6","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000166926.54293.68"},{"key":"2026092109352406000_43.2.531.7","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00169.2007"},{"key":"2026092109352406000_43.2.531.8","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00286.2010"},{"key":"2026092109352406000_43.2.531.9","first-page":"139","article-title":"[Effect of p21 gene transfection mediated by replication deficient adenovirus on the pulmonary hypertensive rat model]","volume":"46","author":"Chen","year":"2008","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"2026092109352406000_43.2.531.10","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.25.5.4592"},{"key":"2026092109352406000_43.2.531.11","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000188211.83193.1a"},{"key":"2026092109352406000_43.2.531.12","doi-asserted-by":"crossref","unstructured":"Ravi Y Selvendiran K Meduru S . Dysregulation of PTEN in cardiopulmonary vascular remodeling induced by pulmonary hypertension. Cell Biochem Biophys 2011 [In press DOI: 10.1007\/s12013-011-9332-z].","DOI":"10.1007\/s12013-011-9332-z"},{"key":"2026092109352406000_43.2.531.13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.963314"},{"key":"2026092109352406000_43.2.531.14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101812"},{"key":"2026092109352406000_43.2.531.15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00654.2011"},{"key":"2026092109352406000_43.2.531.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610467104"},{"key":"2026092109352406000_43.2.531.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2006.08.011"},{"key":"2026092109352406000_43.2.531.18","doi-asserted-by":"publisher","DOI":"10.1038\/35010517"},{"key":"2026092109352406000_43.2.531.19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610672200"},{"key":"2026092109352406000_43.2.531.20","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21246"},{"key":"2026092109352406000_43.2.531.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(01)00123-9"},{"key":"2026092109352406000_43.2.531.22","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1549"},{"key":"2026092109352406000_43.2.531.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.041"},{"key":"2026092109352406000_43.2.531.24","doi-asserted-by":"publisher","DOI":"10.1038\/372786a0"},{"key":"2026092109352406000_43.2.531.25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009063200"},{"key":"2026092109352406000_43.2.531.26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.23.13649"},{"key":"2026092109352406000_43.2.531.27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.29.17437"},{"key":"2026092109352406000_43.2.531.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.018"},{"key":"2026092109352406000_43.2.531.29","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2010.489548"},{"key":"2026092109352406000_43.2.531.30","unstructured":"National InstitutesofHealth. Principles of Laboratory Animal Care. Publication No. 85\u201323, revised 1996. Bethesda, MD, 1996."},{"key":"2026092109352406000_43.2.531.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00109-0"},{"key":"2026092109352406000_43.2.531.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.10.020"},{"key":"2026092109352406000_43.2.531.33","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.2.954"},{"key":"2026092109352406000_43.2.531.34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606695200"},{"key":"2026092109352406000_43.2.531.35","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00004-10"},{"key":"2026092109352406000_43.2.531.36","doi-asserted-by":"publisher","DOI":"10.1002\/stem.23"},{"key":"2026092109352406000_43.2.531.37","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00255-6"},{"key":"2026092109352406000_43.2.531.38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204786"},{"key":"2026092109352406000_43.2.531.39","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.5.1565-1572.2001"},{"key":"2026092109352406000_43.2.531.40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404307200"},{"key":"2026092109352406000_43.2.531.41","doi-asserted-by":"publisher","DOI":"10.1159\/000329593"},{"key":"2026092109352406000_43.2.531.42","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208469"},{"key":"2026092109352406000_43.2.531.43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807761200"},{"key":"2026092109352406000_43.2.531.44","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200503021"},{"key":"2026092109352406000_43.2.531.45","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3432006pe30"},{"key":"2026092109352406000_43.2.531.46","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3959"},{"key":"2026092109352406000_43.2.531.47","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.bbrc.2010.07.064","article-title":"XIAP is essential for shear stress-enhanced Tyr-576 phosphorylation of FAK","volume":"399","author":"Ahn","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"2026092109352406000_43.2.531.48","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1096\/fasebj.12.12.1135","article-title":"Activation of PDGF receptor \u03b1 in vascular smooth muscle cells by mechanical stress","volume":"12","author":"Hu","year":"1998","journal-title":"FASEB J"},{"key":"2026092109352406000_43.2.531.49","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.36.3.319"},{"key":"2026092109352406000_43.2.531.50","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000154548.16191.2F"},{"key":"2026092109352406000_43.2.531.51","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00286.2010"},{"key":"2026092109352406000_43.2.531.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.11.031"},{"key":"2026092109352406000_43.2.531.53","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.064212"},{"key":"2026092109352406000_43.2.531.54","doi-asserted-by":"publisher","DOI":"10.1126\/stke.120pe22"},{"key":"2026092109352406000_43.2.531.55","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3261fje"},{"key":"2026092109352406000_43.2.531.56","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000141576.39579.23"},{"key":"2026092109352406000_43.2.531.57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030678"},{"key":"2026092109352406000_43.2.531.58","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.632208"},{"key":"2026092109352406000_43.2.531.59","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.7.558"},{"key":"2026092109352406000_43.2.531.60","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000081595.25297.1B"},{"key":"2026092109352406000_43.2.531.61","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00692.2004"},{"key":"2026092109352406000_43.2.531.62","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000152390.99806.A5"},{"key":"2026092109352406000_43.2.531.63","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00659.2005"},{"key":"2026092109352406000_43.2.531.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.07.070"},{"key":"2026092109352406000_43.2.531.65","doi-asserted-by":"crossref","first-page":"H1695","DOI":"10.1152\/ajpheart.2000.278.5.H1695","article-title":"Endothelin-induced cardiac myocyte hypertrophy: role for focal adhesion kinase","volume":"278","author":"Eble","year":"2000","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2026092109352406000_43.2.531.66","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909099199"},{"key":"2026092109352406000_43.2.531.67","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2007.08.006"},{"key":"2026092109352406000_43.2.531.68","unstructured":"Study Of PF-00562271, including patients with pancreatic, head and neck, prostatic neoplasms. http:\/\/clinicaltrials.gov\/show\/NCT00666926 Last accessed: March 14, 2013, 2013."}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/09031936.00181312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:36:40Z","timestamp":1790008600000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/09031936.00181312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,11]]},"references-count":68,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,1,31]]},"published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1183\/09031936.00181312"],"URL":"https:\/\/doi.org\/10.1183\/09031936.00181312","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,11]]}}}