{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:45:58Z","timestamp":1793385958280,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100015760","name":"Inserm Transfert","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015760","id-type":"DOI","asserted-by":"publisher"}]},{"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\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chancellerie des Universit\u00e9s"},{"DOI":"10.13039\/100012019","name":"Fondation du Souffle","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015760","name":"Inserm Transfert","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015760","id-type":"DOI","asserted-by":"crossref"}]},{"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\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chancellerie des Universit\u00e9s"},{"DOI":"10.13039\/100012019","name":"Fondation du Souffle","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012019","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Hepatopulmonary syndrome (HPS) is a severe complication of liver diseases characterized by abnormal dilation of pulmonary vessels, resulting in impaired oxygenation. Recent research highlights the pivotal role of liver-produced BMP-9 (bone morphogenetic protein-9) in maintaining pulmonary vascular integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to investigate the involvement of BMP-9 in human and experimental HPS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Circulating BMP-9 levels were measured in 63 healthy control subjects and 203 patients with cirrhosis with or without HPS. Two animal models of portal hypertension were employed: common bile duct ligation with cirrhosis and long-term partial portal vein ligation without cirrhosis. Additionally, the therapeutic effect of low-dose BMP activator FK506 was investigated, and the pulmonary vascular phenotype of BMP-9\u2013knockout rats was analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Patients with HPS related to compensated cirrhosis exhibited lower levels of circulating BMP-9 compared with patients without HPS. Patients with severe cirrhosis exhibited consistently low levels of BMP-9. HPS characteristics were observed in animal models, including intrapulmonary vascular dilations and an increase in the alveolar-arterial gradient. HPS development in both rat models correlated with reduced intrahepatic BMP-9 expression, decreased circulating BMP-9 level and activity, and impaired pulmonary BMP-9 endothelial pathway. Daily treatment with FK506 for 2\u2009weeks restored the BMP pathway in the lungs, alleviating intrapulmonary vascular dilations and improving gas exchange impairment. Furthermore, BMP-9\u2013knockout rats displayed a pulmonary HPS phenotype, supporting its role in disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study findings suggest that portal hypertension\u2013induced loss of BMP-9 signaling contributes to HPS development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202307-1289oc","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T14:59:25Z","timestamp":1713279565000},"page":"648-661","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":30,"title":["Disrupted BMP-9 Signaling Impairs Pulmonary Vascular Integrity in Hepatopulmonary Syndrome"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3132-8706","authenticated-orcid":false,"given":"Fabien","family":"Robert","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Unit\u00e9 Mixte de Recherche en Sant\u00e9 (UMR_S) 999 \u201cHypertension Pulmonaire: Physiopathologie et Innovation Th\u00e9rapeutique (HPPIT)\u201d, Le Kremlin-Bic\u00eatre, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMR_S 999 \u201cHPPIT\u201d, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Caroline","family":"Certain","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Unit\u00e9 Mixte de Recherche en Sant\u00e9 (UMR_S) 999 \u201cHypertension Pulmonaire: Physiopathologie et Innovation Th\u00e9rapeutique (HPPIT)\u201d, Le Kremlin-Bic\u00eatre, France"},{"name":"Institut National de la Sant\u00e9 et de la 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