{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:15Z","timestamp":1792785855555,"version":"4.5.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Medical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Grenoble Alpes"},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["EQU202003010188"],"award-info":[{"award-number":["EQU202003010188"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Association Maladie de Rendu-Osler"},{"name":"French National Agency","award":["ANR-17-CE14-0006"],"award-info":[{"award-number":["ANR-17-CE14-0006"]}]},{"name":"GRAL"},{"name":"Chemistry Biology Health","award":["ANR-17-EURE-003"],"award-info":[{"award-number":["ANR-17-EURE-003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>BMP9 is a high affinity ligand of ALK1 and endoglin receptors that are mutated in the rare genetic vascular disorder hereditary hemorrhagic telangiectasia (HHT). We have previously shown that loss of Bmp9 in the 129\/Ola genetic background leads to spontaneous liver fibrosis via capillarization of liver sinusoidal endothelial cells (LSEC) and kidney lesions. We aimed to decipher the molecular mechanisms downstream of BMP9 to better characterize its role in vascular homeostasis in different organs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>For this, we performed an RNA-seq analysis on LSEC from adult WT and Bmp9-KO mice and identified over 2000 differentially expressed genes. Gene ontology analysis showed that Bmp9 deletion led to a decrease in BMP and Notch signalling, but also LSEC capillary identity while increasing their cell cycle. The gene ontology term \u2018glomerulus development\u2019 was also negatively enriched in Bmp9-KO mice vs. WT supporting a role for BMP9 in kidney vascularization. Through different imaging approaches (electron microscopy, immunostainings), we found that loss of Bmp9 led to vascular enlargement of the glomeruli capillaries associated with alteration of podocytes. Importantly, we also showed for the first time that the loss of Bmp9 led to spontaneous arteriovenous malformations (AVMs) in the liver, gastrointestinal tract, and uterus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Altogether, these results demonstrate that BMP9 plays an important role in vascular quiescence both locally in the liver by regulating endothelial capillary differentiation markers and cell cycle but also at distance in many organs via its presence in the circulation. It also reveals that loss of Bmp9 is sufficient to induce spontaneous AVMs, supporting a key role for BMP9 in the pathogenesis of HHT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvae052","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T16:38:01Z","timestamp":1710866281000},"page":"782-795","source":"Crossref","is-referenced-by-count":17,"title":["BMP9 is a key player in endothelial identity and its loss is sufficient to induce arteriovenous malformations"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3301-9504","authenticated-orcid":false,"given":"Agnes","family":"Desroches-Castan","sequence":"first","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dzenis","family":"Koca","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3830-3421","authenticated-orcid":false,"given":"Hequn","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5380-4422","authenticated-orcid":false,"given":"Caroline","family":"Roelants","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-4189","authenticated-orcid":false,"given":"L\u00e9a","family":"Resmini","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, PARCC , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7572-173X","authenticated-orcid":false,"given":"Nicolas","family":"Ricard","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5252-754X","authenticated-orcid":false,"given":"Claire","family":"Bouvard","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Chaumontel","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6062-5905","authenticated-orcid":false,"given":"Pierre-Louis","family":"Tharaux","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, PARCC , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0076-8007","authenticated-orcid":false,"given":"Emmanuelle","family":"Tillet","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6849-7824","authenticated-orcid":false,"given":"Christophe","family":"Battail","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8107-6987","authenticated-orcid":false,"given":"Olivia","family":"Lenoir","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, PARCC , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-7030","authenticated-orcid":false,"given":"Sabine","family":"Bailly","sequence":"additional","affiliation":[{"name":"Laboratoire Biosant\u00e9 U1292, Universit\u00e9 Grenoble Alpes, Inserm, CEA , 17 avenue des Martyrs, 38054 Grenoble , 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