{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:07:09Z","timestamp":1785409629726,"version":"3.56.0"},"reference-count":0,"publisher":"European Respiratory Society (ERS)","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL158998-01A1"],"award-info":[{"award-number":["R01HL158998-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL160963"],"award-info":[{"award-number":["R01HL160963"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL172043"],"award-info":[{"award-number":["R01HL172043"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL173203-01"],"award-info":[{"award-number":["R01HL173203-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R03TR004673"],"award-info":[{"award-number":["R03TR004673"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23TPA1061690"],"award-info":[{"award-number":["23TPA1061690"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002590","name":"American Lung Association","doi-asserted-by":"publisher","award":["1056600"],"award-info":[{"award-number":["1056600"]}],"id":[{"id":"10.13039\/100002590","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2026,5,23]]},"abstract":"\n Background<\/jats:title>\n Despite advances in therapy, pulmonary arterial hypertension (PAH) remains progressive with poor survival. Although dysregulation of Bone Morphogenetic Protein (BMP) signaling is central to PAH, key modulators of this pathway remain incompletely defined.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To identify the role of BMP3 in pulmonary vascular homeostasis and PAH.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n BMP3 expression was assessed in experimental pulmonary hypertension (PH) and in pulmonary vascular cells and plasma from PAH patients. In vitro studies were performed in human pulmonary artery smooth muscle cells (hPASMCs) and endothelial cells (hPAECs). Global and SMC-specific\n Bmp3<\/jats:italic>\n -deficient mice were generated. Recombinant BMP3 and adeno-associated viruses (AAV) were used to overexpress BMP3 in animal models of PAH.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n BMP3 is predominantly expressed in PASMCs and is consistently downregulated in experimental and human PAH. Secreted BMP3 from PAH-PASMCs and circulating BMP3 levels in PAH patients were significantly reduced. Functionally, PASMC-derived BMP3 inhibited the migration and proliferation of PAH-diseased PAEC. In both global and SMC-specific\n Bmp3<\/jats:italic>\n -deficient mice, induction of PAH led to significantly exacerbated disease in middle-aged mice. A recombinant BMP3 prevented and reversed PAH in mice. Furthermore, lung-targeted overexpression of BMP3,\n via<\/jats:italic>\n AAV1-BMP3, reversed pulmonary vascular remodeling and ameliorated cardiac function in both mice and rats. Mechanistically, BMP3 restored the balance between BMP\/SMAD1,5,8 and TGF-\u03b2\/SMAD2,3 signaling, and decreased the expression of cell cycle genes in PAECs.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n BMP3 acts as a paracrine regulator of pulmonary vascular homeostasis and may contribute to the modulation of TGF-\u03b2\/BMP signaling in PAH, highlighting its potential as a therapeutic target.<\/jats:p>\n <\/jats:sec>","DOI":"10.1183\/13993003.02146-2025","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:30:19Z","timestamp":1785407419000},"page":"2502146","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Paracrine action of bone morphogenetic protein 3 in pulmonary arterial hypertension"],"prefix":"10.1183","author":[{"given":"Aymen","family":"Halouani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Mensah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariem","family":"Ben Rhouma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaujia","family":"Athumani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seun","family":"Imani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar A.","family":"Antar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Jankowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Mansoori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyotake","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lahouaria","family":"Hadri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassine","family":"Sassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2026,7,30]]},"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.02146-2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:30:20Z","timestamp":1785407420000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.02146-2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":0,"alternative-id":["10.1183\/13993003.02146-2025"],"URL":"https:\/\/doi.org\/10.1183\/13993003.02146-2025","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}