{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:39:49Z","timestamp":1792690789492,"version":"4.5.0"},"reference-count":8,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>\n              In humans, activin receptor-like kinase 1 (Alk1) deficiency causes arteriovenous malformations (AVMs) in multiple organs, including the brain. Focal\n              <jats:italic>Alk1<\/jats:italic>\n              pan-cellular deletion plus vascular endothelial growth factor stimulation induces brain AVMs in the adult mouse. We hypothesized that deletion of\n              <jats:italic>Alk1<\/jats:italic>\n              in endothelial cell (EC) alone plus focal vascular endothelial growth factor stimulation is sufficient to induce brain AVM in the adult mouse.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              Focal angiogenesis was induced in the brain of 8-week-old\n              <jats:italic>Pdgfb<\/jats:italic>\n              -iCreER;\n              <jats:italic>Alk1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>2f\/2f<\/jats:italic>\n              <\/jats:sup>\n              mice by injection of adeno-associated viral vectors expressing vascular endothelial growth factor. Two weeks later, EC-\n              <jats:italic>Alk1<\/jats:italic>\n              deletion was induced by tamoxifen treatment. Vascular morphology was analyzed, and EC proliferation and dysplasia index (number of vessels with diameter &gt;15 \u03bcm per 200 vessels) were quantified 10 days after tamoxifen administration.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              Tangles of enlarged vessels resembling AVMs were present in the brain angiogenic region of tamoxifen-treated\n              <jats:italic>Pdgfb<\/jats:italic>\n              -iCreER;\n              <jats:italic>Alk1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>2f\/2f<\/jats:italic>\n              <\/jats:sup>\n              mice. Induced brain AVMs were marked by increased dysplasia index (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and EC proliferation clustered within the dysplastic vessels. AVMs were also detected around the ear tag-wound and in other organs.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Deletion of\n              <jats:italic>Alk1<\/jats:italic>\n              in EC in adult mice leads to an increased local EC proliferation during brain angiogenesis and de novo brain AVM.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.113.003655","type":"journal-article","created":{"date-parts":[[2014,1,24]],"date-time":"2014-01-24T04:57:50Z","timestamp":1390539470000},"page":"900-902","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":91,"title":["De Novo Cerebrovascular Malformation in the Adult Mouse After Endothelial\n            <i>Alk1<\/i>\n            Deletion and Angiogenic Stimulation"],"prefix":"10.1161","volume":"45","author":[{"given":"Wanqiu","family":"Chen","sequence":"first","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengda","family":"Sun","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenying","family":"Han","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Jun","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Camus","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamta","family":"Wankhede","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Mao","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Arnold","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Young","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Su","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research (W.C., Z.H., K.J., M.C., M.W., L.M., W.L.Y., H.S.), Departments of Radiology (Z.S.), Pediatrics (T.A.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22348"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000095246.40391.3b"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-08-107359"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20367"},{"key":"e_1_3_4_6_2","first-page":"3487","article-title":"Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia.","volume":"119","author":"Park SO","year":"2009","unstructured":"Park SO, Wankhede M, Lee YJ, Choi EJ, Fliess N, Choe SW, et al.. Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia. J Clin Invest. 2009;119:3487\u20133496.","journal-title":"J Clin Invest"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-010-0020-x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.112.300485"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.111.647024"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.113.003655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:34:43Z","timestamp":1715610883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.113.003655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3]]},"references-count":8,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1161\/STROKEAHA.113.003655"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.113.003655","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3]]},"assertion":[{"value":"2013-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-12-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}