{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:50:00Z","timestamp":1791989400577,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-08-GENOPAT-004"],"award-info":[{"award-number":["ANR-08-GENOPAT-004"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with vascular remodeling and a proliferative disorder in pulmonary artery smooth muscle cells (PASMCs) that has been variably described as having neoplastic features. To decode the phenotype of PASMCs in IPAH, PASMCs from explanted lungs of patients with IPAH (IPAH-PASMCs) and from controls (C-PASMCs) were cultured. The IPAH-PASMCs grew faster than the controls; however, both growth curves plateaued, suggesting contact inhibition in IPAH cells. No proliferation was seen without stimulation with exogenous growth factors, suggesting that IPAH cells are incapable of self-sufficient growth. IPAH-PASMCs were more resistant to apoptosis than C-PASMCs, consistent with the increase in the Bcl2\/Bax ratio. As cell replication is governed by telomere length, these parameters were assessed jointly. Compared to C-PASMCs, IPAH-PASMCs had longer telomeres, but a limited replicative capacity. Additionally, it was noted that IPAH-PASMCs had a shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis. As DNA damage and genomic instability are strongly implicated in IPAH development a comparative genomic hybridization was performed on genomic DNA from PASMCs which showed multiple break-points unaffected by IPAH severity. Activation of DNA damage\/repair factors (\u03b3H2AX, p53, and GADD45) in response to cisplatin was measured. All proteins showed lower phosphorylation in IPAH samples than in controls, suggesting that the cells were resistant to DNA damage. Despite the cancer-like processes that are associated with end-stage IPAH-PASMCs, we identified no evidence of self-sufficient proliferation in these cells\u2014the defining feature of neoplasia.<\/jats:p>","DOI":"10.3390\/ijms20143575","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T11:07:28Z","timestamp":1563793648000},"page":"3575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Smooth Muscle Phenotype in Idiopathic Pulmonary Hypertension: Hyper-Proliferative but not Cancerous"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7730-2427","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Perros","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de M\u00e9decine, 94270 Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Centre de R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire S\u00e9v\u00e8re, D\u00e9partement Hospitalo-Universitaire Thorax Innovation, Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital de Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Unit\u00e9 Mixte de Recherche 999, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Paris-Sud, Laboratoire d\u2019Excellence en Recherche sur le M\u00e9dicament et l\u2019Innovation Th\u00e9rapeutique, 92350 Le Plessis Robinson, France"},{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Laval University, Montr\u00e9al, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1806-5120","authenticated-orcid":false,"given":"Pierre","family":"Sentenac","sequence":"additional","affiliation":[{"name":"PhyMedExp, University of Montpellier, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, 34295 Montpellier, France"},{"name":"Department of An\u00e6sthesiology and Critical Care Medicine, Arnaud de Villeneuve Teaching Hospital, Montpellier University School of Medicine, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Boulate","sequence":"additional","affiliation":[{"name":"Department of Thoracic and Vascular Surgery, Marie Lannelongue Hospital, 92350 Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9goire","family":"Manaud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de M\u00e9decine, 94270 Kremlin-Bic\u00eatre, France"},{"name":"Unit\u00e9 Mixte de Recherche 999, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Paris-Sud, Laboratoire d\u2019Excellence en Recherche sur le M\u00e9dicament et l\u2019Innovation Th\u00e9rapeutique, 92350 Le Plessis Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Kotsimbos","sequence":"additional","affiliation":[{"name":"Alfred Health, Monash University, VIC 3004 Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lecerf","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de M\u00e9decine, 94270 Kremlin-Bic\u00eatre, France"},{"name":"Unit\u00e9 Mixte de Recherche 999, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Paris-Sud, Laboratoire d\u2019Excellence en Recherche sur le M\u00e9dicament et l\u2019Innovation Th\u00e9rapeutique, 92350 Le Plessis Robinson, France"},{"name":"Research Department, Marie Lannelongue Hospital, 92350 Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia","family":"Lamrani","sequence":"additional","affiliation":[{"name":"Research Department, Marie Lannelongue Hospital, 92350 Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie","family":"Fadel","sequence":"additional","affiliation":[{"name":"Research Department, Marie Lannelongue Hospital, 92350 Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Mercier","sequence":"additional","affiliation":[{"name":"Research Department, Marie Lannelongue Hospital, 92350 Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-7563","authenticated-orcid":false,"given":"Arturo","family":"Londono-Vallejo","sequence":"additional","affiliation":[{"name":"Research Department, Marie Lannelongue Hospital, 92350 Le Plessis-Robinson, France"},{"name":"Institut Curie, PSL Research University, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 3244, Telomere and cancer lab, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Humbert","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, Facult\u00e9 de M\u00e9decine, 94270 Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Centre de R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire S\u00e9v\u00e8re, D\u00e9partement Hospitalo-Universitaire Thorax Innovation, Service de Pneumologie et R\u00e9animation Respiratoire, H\u00f4pital de Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Unit\u00e9 Mixte de Recherche 999, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Paris-Sud, Laboratoire d\u2019Excellence en Recherche sur le M\u00e9dicament et l\u2019Innovation Th\u00e9rapeutique, 92350 Le Plessis Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0374-019X","authenticated-orcid":false,"given":"Saadia","family":"Eddahibi","sequence":"additional","affiliation":[{"name":"PhyMedExp, University of Montpellier, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, 34295 Montpellier, France"},{"name":"Research Department, Marie Lannelongue Hospital, 92350 Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1750-1172-8-97","article-title":"Pulmonary arterial hypertension","volume":"8","author":"Montani","year":"2013","journal-title":"Orphanet J. 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