{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:23:03Z","timestamp":1790504583042,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:00:00Z","timestamp":1508198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"Objective<\/jats:title>To elucidate the role of gene candidates involved in pulmonary hypertension (PH<\/jats:styled-content>) associated with systemic sclerosis (SS<\/jats:styled-content>c).<\/jats:p><\/jats:sec>Methods<\/jats:title>Gene candidates were identified through microarray experiments performed on Affymetrix GeneChip Human Exon 1.0 ST<\/jats:styled-content> arrays in endothelial progenitor cell (EPC<\/jats:styled-content>)\u2013derived endothelial cells (EC<\/jats:styled-content>s) obtained from patients with SS<\/jats:styled-content>c\u2010associated PH<\/jats:styled-content>, patients with SS<\/jats:styled-content>c without PH<\/jats:styled-content>, and healthy control subjects. Expression of identified gene candidates was assessed by quantitative sandwich enzyme\u2010linked immunosorbent assay in the serum, and by immunohistochemistry in lesional lung tissue. The functional importance of the identified gene candidates was then evaluated in fos<\/jats:italic>\u2010related antigen 2\u2013transgenic (Fra\u20102\u2013Tg) mice that spontaneously develop SS<\/jats:styled-content>c\u2010like features associated with an intense pulmonary vascular remodeling.<\/jats:p><\/jats:sec>Results<\/jats:title>Microarray experiments revealed that the matrix metalloproteinase 10 (MMP<\/jats:styled-content>\u201010) gene was the top up\u2010regulated gene in SS<\/jats:styled-content>c\u2010associated PH EPC<\/jats:styled-content>\u2010derived EC<\/jats:styled-content>s. Circulating serum proMMP<\/jats:styled-content>10 concentrations were markedly increased in patients with SS<\/jats:styled-content>c\u2010associated PH<\/jats:styled-content> compared to SS<\/jats:styled-content>c patients without PH<\/jats:styled-content> and healthy controls. Consistent with these observations, a strong MMP<\/jats:styled-content>10 staining of the thickened wall of distal pulmonary arteries was found both in the lungs of patients with SS<\/jats:styled-content>c\u2010associated PH<\/jats:styled-content> and in the lungs of Fra\u20102\u2013Tg mice. Daily treatment of Fra\u20102\u2013Tg mice with neutralizing anti\u2010MMP<\/jats:styled-content>10 antibodies did not significantly affect the development and severity of pulmonary fibrosis, but did reverse established PH<\/jats:styled-content> and markedly reduced pulmonary vascular remodeling by reducing cell proliferation, cell survival, and the platelet\u2010derived growth factor signaling axis.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Gene expression profiling of EPC<\/jats:styled-content>\u2010derived EC<\/jats:styled-content>s identified MMP<\/jats:styled-content>10 as a novel candidate gene in SS<\/jats:styled-content>c\u2010associated PH<\/jats:styled-content>. MMP<\/jats:styled-content>10 is overexpressed in the serum and pulmonary arteries of patients with SS<\/jats:styled-content>c\u2010associated PH<\/jats:styled-content>, and its blockade alleviates PH<\/jats:styled-content> in the Fra\u20102\u2013Tg mouse model. MMP<\/jats:styled-content>10 appears to be a prospective treatment target for this devastating disorder.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40229","type":"journal-article","created":{"date-parts":[[2017,8,13]],"date-time":"2017-08-13T22:06:36Z","timestamp":1502661996000},"page":"2209-2221","source":"Crossref","is-referenced-by-count":24,"title":["Role of Stromelysin 2 (Matrix Metalloproteinase 10) as a Novel Mediator of Vascular Remodeling Underlying Pulmonary Hypertension Associated With Systemic Sclerosis"],"prefix":"10.1002","volume":"69","author":[{"given":"J\u00e9r\u00f4me","family":"Avouac","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 INSERM U1016 and CNRS UMR8104 Institut Cochin, and Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Service de Rhumatologie A, H\u00f4pital Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Guignabert","sequence":"additional","affiliation":[{"name":"Inserm UMR S 999, Plessis Robinson, France, and Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Hoffmann\u2010Vold","sequence":"additional","affiliation":[{"name":"Oslo University Hospital\u2013Rikshospitalet and Institute of Clinical Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 INSERM U1016 and CNRS UMR8104 Institut Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dorfmuller","sequence":"additional","affiliation":[{"name":"Inserm UMR S 999, Plessis Robinson, France, and Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Pezet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 INSERM U1016 and CNRS UMR8104 Institut Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Amar","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 INSERM U1016 and CNRS UMR8104 Institut Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ly","family":"Tu","sequence":"additional","affiliation":[{"name":"Inserm UMR S 999, Plessis Robinson, France, and Universit\u00e9 Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Van Wassenhove","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 INSERM U1016 and CNRS UMR8104 Institut Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my","family":"Sadoine","sequence":"additional","affiliation":[{"name":"EA 2496 Pathologie Imagerie et Bioth\u00e9rapies Orofaciales UFR Odontologie Universit\u00e9 Paris Descartes and PIDV PRES Sorbonne Paris Cit\u00e9 Montrouge France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Launay","sequence":"additional","affiliation":[{"name":"M\u00e9decine Interne, Hopital Huriez Universit\u00e9 de Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Elhai","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 INSERM U1016 and CNRS UMR8104 Institut Cochin, and Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Service de Rhumatologie A, H\u00f4pital Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Cauvet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 INSERM U1016 and CNRS UMR8104 Institut Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"Sanofi Genzyme Framingham Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Resnick","sequence":"additional","affiliation":[{"name":"Sanofi Genzyme Framingham Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hachulla","sequence":"additional","affiliation":[{"name":"M\u00e9decine Interne, Hopital Huriez Universit\u00e9 de Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8yvind","family":"Molberg","sequence":"additional","affiliation":[{"name":"Oslo University Hospital\u2013Rikshospitalet and Institute of Clinical Medicine University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Kahan","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Service de Rhumatologie A, H\u00f4pital Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Humbert","sequence":"additional","affiliation":[{"name":"Inserm UMR S 999 Plessis Robinson, France, and Universit\u00e9 Paris\u2010Sud Universit\u00e9 Paris\u2010Saclay and AP\u2010HP Service de Pneumologie H\u00f4pital Bic\u00eatre Le Kremlin Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Allanore","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 INSERM U1016 and CNRS UMR8104 Institut Cochin, and Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Service de Rhumatologie A, H\u00f4pital Cochin Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.100245"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.911818"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.114264"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01032-2015"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00057010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.006974"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-0862"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.004555"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.025"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.082131"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23968"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1396"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.09.059"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30536"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200810-1662OC"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/2045-8932.78095"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1523512113"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00362.2011"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.855114"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200940"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39166"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.140047"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00199.2009"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.007469"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00193014"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201402-0322OC"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.41.4.467"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201759"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208213"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22175"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3315"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.341156"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201006-0905OC"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00209911"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1078\/0344-0338-00273"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00072504"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00383.2014"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39476"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-5231(05)70282-3"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2007.12.010"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.259"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000196241.96759.71"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.6_suppl.572S"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.16.1.28"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-015-0280-9"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-6-128"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2012.719500"}],"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40229","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40229","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:07:19Z","timestamp":1759939639000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,17]]},"references-count":48,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1002\/art.40229"],"URL":"https:\/\/doi.org\/10.1002\/art.40229","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,17]]}}}