{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:55:10Z","timestamp":1790794510195,"version":"4.1.0"},"reference-count":14,"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":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>\n                    Hereditary hemorrhagic telangiectasia (HHT) is characterized by fragile, enlarged vessels with arteriovenous connections, which can form arteriovenous malformations (AVMs) that are prone to rupture. It is driven by mutations in TGF\u2011\u03b2 pathway genes that disrupt endothelial cell responses and blood vessel remodeling. Two studies published in this issue of the\n                    <jats:italic>JCI<\/jats:italic>\n                    identify c\u2011KIT as a central mediator of HHT vascular pathology. Gahn et al. showed that SMAD4 loss derepressed c\u2011KIT, whose activity in the junctional mechanosensory receptor complex of endothelial cells reset the fluid shear stress set point to drive maladaptive vascular remodeling. Drap\u00e9 et al. demonstrated that ALK1 loss in a mouse model of HHT induced a regional pro\u2011angiogenic c\u2011KIT\n                    <jats:sup>+<\/jats:sup>\n                    endothelial state in brain AVMs. Both studies showed that pharmacologic c-KIT inhibition mitigated disease, revealing an unexpected, potentially ligand\u2011independent role for c\u2011KIT and highlighting a promising therapeutic target.\n                  <\/jats:p>","DOI":"10.1172\/jci210364","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:01:22Z","timestamp":1790791282000},"source":"Crossref","is-referenced-by-count":0,"title":["c-KIT expands the tool kit for treating arteriovenous malformation"],"prefix":"10.1172","volume":"136","author":[{"given":"Ruilin","family":"Wu","sequence":"first","affiliation":[{"name":"Peter Munk Cardiac Centre, UHN Research Institutes, University Health Network, Toronto, Ontario, Canada."},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0640-7277","authenticated-orcid":true,"given":"Jason E.","family":"Fish","sequence":"additional","affiliation":[{"name":"Peter Munk Cardiac Centre, UHN Research Institutes, University Health Network, Toronto, Ontario, Canada."},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/81634"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3528"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI168352"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature03952"},{"issue":"19","key":"B5","article-title":"Loss of Smad4 drives vascular malformations via c-KIT\u2013dependent high\u2013fluid shear stress mimicry","volume":"136","author":"Gahn","year":"2026","journal-title":"J Clin Invest"},{"issue":"19","key":"B6","doi-asserted-by":"crossref","DOI":"10.1172\/JCI197587","article-title":"Targeting KIT prevents brain arteriovenous malformations driven by ALK1-deficient angiogenic endothelial cells","volume":"136","author":"Drap\u00e9","year":"2026","journal-title":"J Clin Invest"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae058"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311643200"},{"key":"B9","doi-asserted-by":"crossref","unstructured":"Bartoletti AP, et al. Modeling somatic second-hit mutations in novel mouse models of hereditary hemorrhagic telangiectasia [preprint]. https:\/\/doi.org\/10.64898\/2026.02.15.706014 Posted on bioRxiv February 22, 2026","DOI":"10.64898\/2026.02.15.706014"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007258"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609324"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709449"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201505433"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature17178"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/210364\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:03:00Z","timestamp":1790791380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/210364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":14,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,8,11]]},"published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1172\/JCI210364"],"URL":"https:\/\/doi.org\/10.1172\/jci210364","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"e210364"}}