{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:03:06Z","timestamp":1791165786665,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"French National Institute for Health and Medical Research"},{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012681","name":"CNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012681","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Paris-Sud"},{"DOI":"10.13039\/501100007241","name":"Universit\u00e9 Paris-Saclay","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007241","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003768","name":"Universit\u00e9 de Strasbourg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Marie Lannelongue Hospital"},{"name":"French National Agency for Research","award":["ANR-16-CE17-0014"],"award-info":[{"award-number":["ANR-16-CE17-0014"]}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["DEQ20150331712"],"award-info":[{"award-number":["DEQ20150331712"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"name":"D\u00e9partement Hospitalo-Universitaire"},{"name":"Thorax Innovation"},{"name":"Assistance Publique-H\u00f4pitaux de Paris"},{"name":"Service de Pneumologie, Centrede R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire S\u00e9v\u00e8re, the LABEX Medalis","award":["ANR-10-LABX-0034"],"award-info":[{"award-number":["ANR-10-LABX-0034"]}]},{"DOI":"10.13039\/501100011879","name":"LabEx LERMIT","doi-asserted-by":"publisher","award":["ANR-10-LABX-0033"],"award-info":[{"award-number":["ANR-10-LABX-0033"]}],"id":[{"id":"10.13039\/501100011879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims\u2003<\/jats:title>\n                  <jats:p>The progressive accumulation of cells in pulmonary vascular walls is a key pathological feature of pulmonary arterial hypertension (PAH) that results in narrowing of the vessel lumen, but treatments targeting this mechanism are lacking. The C-X-C motif chemokine 12 (CXCL12) appears to be crucial in these processes. We investigated the activity of two CXCL12 neutraligands on experimental pulmonary hypertension (PH), using two complementary animal models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results\u2003<\/jats:title>\n                  <jats:p>Male Wistar rats were injected with monocrotaline (MCT) or were subjected to SU5416 followed by 3-week hypoxia to induce severe PH. After PH establishment, assessed by pulsed-wave Doppler echocardiography, MCT-injected or SU5416 plus chronic hypoxia (SuHx) rats were randomized to receive CXCL12 neutraligands chalcone 4 or LIT-927 (100\u2009mg\/kg\/day), the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100 (5\u2009mg\/kg\/day), or vehicle, for 2 or 3\u2009weeks, respectively. At the end of these treatment periods, echocardiographic and haemodynamic measurements were performed and tissue samples were collected for protein expression and histological analysis. Daily treatment of MCT-injected or SuHx rats with established PH with chalcone 4 or LIT-927 partially reversed established PH, reducing total pulmonary vascular resistance, and remodelling of pulmonary arterioles. Consistent with these observations, we found that neutralization of CXCL12 attenuates right ventricular hypertrophy, pulmonary vascular remodelling, and decreases pulmonary artery smooth muscle cell (PA-SMC) proliferation in lungs of MCT-injected rats and SuHx rats. Importantly, CXCL12 neutralization with either chalcone 4 or LIT-927 inhibited the migration of PA-SMCs and pericytes in vitro with a better efficacy than AMD3100. Finally, we found that CXCL12 neutralization decreases vascular pericyte coverage and macrophage infiltration in lungs of both MCT-injected and SuHx rats.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion\u2003<\/jats:title>\n                  <jats:p>We report here a greater beneficial effect of CXCL12 neutralization vs. the conventional CXCR4 blockade with AMD3100 in the MCT and SuHx rat models of severe PH, supporting a role for CXCL12 in the progression of vascular complications in PH and opening to new therapeutic options.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvz153","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T19:10:26Z","timestamp":1559589026000},"page":"686-697","source":"Crossref","is-referenced-by-count":88,"title":["Neutralization of CXCL12 attenuates established pulmonary hypertension in rats"],"prefix":"10.1093","volume":"116","author":[{"given":"Jennifer","family":"Bordenave","sequence":"first","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, 133 Avenue de la R\u00e9sistance, 92350 Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Thuillet","sequence":"first","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, 133 Avenue de la R\u00e9sistance, 92350 Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ly","family":"Tu","sequence":"first","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, 133 Avenue de la R\u00e9sistance, 92350 Le Plessis-Robinson, 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d\u2019Innovation Th\u00e9rapeutique, UMR7200 CNRS\/Universit\u00e9 de Strasbourg and LabEx MEDALIS, Facult\u00e9 de Pharmacie, 74 route du Rhin, 67412 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-747X","authenticated-orcid":false,"given":"Alice","family":"Huertas","sequence":"first","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, 133 Avenue de la R\u00e9sistance, 92350 Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"AP-HP, Service de Pneumologie, Centre de R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire S\u00e9v\u00e8re, DHU Thorax Innovation, H\u00f4pital Bic\u00eatre, 94270 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Savale","sequence":"first","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie 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CNRS\/Universit\u00e9 de Strasbourg and LabEx MEDALIS, Facult\u00e9 de Pharmacie, 74 route du Rhin, 67412 Illkirch, France"},{"name":"Biotechnologie et Signalisation Cellulaire, Ecole Sup\u00e9rieure de Biotechnologie de Strasbourg, UMR 7242 CNRS\/Universit\u00e9 de Strasbourg, 67400 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8252-9199","authenticated-orcid":false,"given":"Dominique","family":"Bonnet","sequence":"first","affiliation":[{"name":"Laboratoire d\u2019Innovation Th\u00e9rapeutique, UMR7200 CNRS\/Universit\u00e9 de Strasbourg and LabEx MEDALIS, Facult\u00e9 de Pharmacie, 74 route du Rhin, 67412 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-2892","authenticated-orcid":false,"given":"Marc","family":"Humbert","sequence":"first","affiliation":[{"name":"INSERM UMR_S 999, H\u00f4pital Marie Lannelongue, 133 Avenue de la R\u00e9sistance, 92350 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