{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:26:55Z","timestamp":1790836015446,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research","award":["202403PJT-517269"],"award-info":[{"award-number":["202403PJT-517269"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Canadian Institutes of Health Research","award":["202203PJT-183658"],"award-info":[{"award-number":["202203PJT-183658"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Canadian Institutes of Health Research","award":["2019PJT-165871"],"award-info":[{"award-number":["2019PJT-165871"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>\n                    Hereditary hemorrhagic telangiectasia type 2 (HHT2), caused by mutations in\n                    <jats:italic>ACVRL1<\/jats:italic>\n                    (also known as\n                    <jats:italic>ALK1<\/jats:italic>\n                    ), is characterized by brain arteriovenous malformations (bAVMs), abnormal artery\u2013vein connections for which treatment options remain limited. Despite evidence of endothelial cell (EC) heterogeneity, its role in bAVM pathogenesis remains poorly defined. Using EC-specific inducible\n                    <jats:italic>Alk1<\/jats:italic>\n                    -knockout mice (\n                    <jats:italic>Alk1iECKO<\/jats:italic>\n                    ) and regionally resolved single-cell RNA sequencing, we showed that loss of ALK1 signaling induces bAVMs predominantly in the perineural vascular plexus. This process is driven by the emergence of a KIT\n                    <jats:sup>+<\/jats:sup>\n                    angiogenic EC population with human AVM-like transcriptional features, including tip cell markers and activation of PI3K and KRAS signaling pathways. Cross-species analyses and validation in human samples demonstrated that KIT expression is conserved in ECs from both sporadic and HHT2 bAVMs. Drug-repurposing analysis identified KIT as a top actionable target, and we showed that\n                    <jats:italic>Kit<\/jats:italic>\n                    is directly repressed by BMP9\/ALK1\/SMAD4 signaling. Pharmacological inhibition of KIT reduced angiogenic reprogramming and vascular malformations in vivo without affecting normal vasculature. These findings identify a pathogenic angiogenic EC state and position KIT signaling as a therapeutically actionable pathway in bAVMs.\n                  <\/jats:p>","DOI":"10.1172\/jci197587","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:00:59Z","timestamp":1786464059000},"source":"Crossref","is-referenced-by-count":1,"title":["Targeting KIT prevents brain arteriovenous malformations driven by ALK1-deficient angiogenic endothelial cells"],"prefix":"10.1172","volume":"136","author":[{"given":"Elise","family":"Drap\u00e9","sequence":"first","affiliation":[{"name":"D\u00e9partement De Pharmacologie Et De Physiologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauranne","family":"Carrier","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"D\u00e9partement De Biochimie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-3518","authenticated-orcid":true,"given":"Gael","family":"Cagnone","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atik Rohmana Maftuhatul","family":"Fuad","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"Department of Anatomy and Cell Biology, School of Biomedical Sciences, McGill University, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Bizou","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"D\u00e9partement De Pathologie Et Biologie Cellulaire, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Typhaine","family":"Anquetil","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"D\u00e9partement De Pathologie Et Biologie Cellulaire, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"Department of Anatomy and Cell Biology, School of Biomedical Sciences, McGill University, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halima Drissi","family":"Touzani Walali","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"D\u00e9partement De Pathologie Et Biologie Cellulaire, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Gopinadhan","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick Piet","family":"van Vliet","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel P.","family":"Howard","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mysha","family":"Ibnat","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Andelfinger","sequence":"additional","affiliation":[{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Larriv\u00e9e","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Ophtalmologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre de Recherche de l\u2019H\u00f4pital Maisonneuve-Rosemont, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Dubrac","sequence":"additional","affiliation":[{"name":"D\u00e9partement De Pharmacologie Et De Physiologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"D\u00e9partement De Biochimie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"Department of Anatomy and Cell Biology, School of Biomedical Sciences, McGill University, Montr\u00e9al, Quebec, Canada."},{"name":"D\u00e9partement De Pathologie Et Biologie Cellulaire, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre De Recherche CHU St. Justine, Montr\u00e9al, Quebec, Canada."},{"name":"D\u00e9partement d\u2019Ophtalmologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Centre de Recherche de l\u2019H\u00f4pital Maisonneuve-Rosemont, Montr\u00e9al, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"1","key":"B1","first-page":"3","article-title":"Epidemiological investigation of Rendu-Osler disease in France: its geographical distribution and prevalence","volume":"44","author":"Bideau","year":"1989","journal-title":"Popul"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1999.00398.x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-345"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-189"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.042606"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5366.1086"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.07.004"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2010.07.001"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/neurintsurg-2015-012252"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12235-1"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1552621"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI176379"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2021.07.106"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2022.1006115"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.8"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.046725"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/genes12020174"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098646"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.211037"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.033842"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030488"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.053047"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.054071"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13650"},{"issue":"pt 6","key":"B25","first-page":"1392","article-title":"Endoglin regulates the activation and quiescence of endothelium by participating in canonical and non-canonical TGF-\u03b2 signaling pathways","volume":"126","author":"Park","year":"2013","journal-title":"J Cell Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-021-09785-7"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi7377"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07493-y"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.062952"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.070925"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2026.03.013"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-73373-w"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.363"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nature25739"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948070"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.02.005"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3171\/2017.6.JNS17860"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1996.85.1.0029"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11112876"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00025"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2023.08.024"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-07959-x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.4.1345"},{"issue":"5","key":"B44","first-page":"683","article-title":"Role and significance of c-KIT receptor tyrosine kinase in cancer: a review","volume":"22","author":"Sheikh","year":"2022","journal-title":"Bosn J Basic Med Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03245"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.319385"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007258"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101188"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201603106"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.oa.2015-0040"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr161"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.82855"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317442"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00046.2011"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.09.102"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1113\/JP280572"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2020"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-107359"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/nature09002"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12235-0"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2020.05.010"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/197587\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:02:52Z","timestamp":1790791372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/197587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":64,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,8,11]]},"published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1172\/JCI197587"],"URL":"https:\/\/doi.org\/10.1172\/jci197587","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"article-number":"e197587"}}