{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:10Z","timestamp":1792787590242,"version":"4.5.0"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1R01 HL112626-06A1"],"award-info":[{"award-number":["1R01 HL112626-06A1"]}]},{"DOI":"10.13039\/100008522","name":"University of Illinois at Chicago","doi-asserted-by":"crossref","award":["Start-up funds"],"award-info":[{"award-number":["Start-up funds"]}],"id":[{"id":"10.13039\/100008522","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,5]]},"abstract":"<jats:p>\n                    Arteriovenous malformations (AVMs) are high-flow lesions directly connecting arteries and veins. In the brain, AVM rupture can cause seizures, stroke, and death. Patients with AVMs exhibit reduced coverage of the vessels by pericytes, the mural cells of microvascular capillaries; however, the mechanism underlying this pericyte reduction and its association with AVM pathogenesis remains unknown. Notch signaling has been proposed to regulate critical pericyte functions. We hypothesized that Notch signaling in pericytes is crucial to maintain pericyte homeostasis and prevent AVM formation. We inhibited Notch signaling specifically in perivascular cells and analyzed the vasculature of these mice. The retinal vessels of mice with deficient perivascular Notch signaling developed severe AVMs, together with a significant reduction in pericytes and vascular smooth muscle cells (vSMC) in the arteries, while vSMCs were increased in the veins. Vascular malformations and pericyte loss were also observed in the forebrain of embryonic mice deficient for perivascular Notch signaling. Moreover, the loss of Notch signaling in pericytes downregulated\n                    <jats:italic>Pdgfrb<\/jats:italic>\n                    levels and increased pericyte apoptosis, pointing to a critical role for Notch in pericyte survival. Overall, our findings reveal a mechanism of AVM formation and highlight the Notch signaling pathway as an essential mediator in this process.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.125940","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T11:01:18Z","timestamp":1604487678000},"source":"Crossref","is-referenced-by-count":79,"title":["Deficiency of Notch signaling in pericytes results in arteriovenous malformations"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3394-2427","authenticated-orcid":true,"given":"Taliha","family":"Nadeem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wil","family":"Bogue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8027-7314","authenticated-orcid":true,"given":"Bianca","family":"Bigit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-9377","authenticated-orcid":true,"given":"Henar","family":"Cuervo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1607407"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.07.001"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1117\/1.NPh.2.4.041402"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2946"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.153.3.543"},{"issue":"3","key":"B6","first-page":"362","article-title":"Diabetes and retinal vascular dysfunction","volume":"9","author":"Shin","year":"2014","journal-title":"J Ophthalmic Vis Res"},{"issue":"11","key":"B7","doi-asserted-by":"crossref","DOI":"10.15252\/embr.201948070","article-title":"Emerging links between cerebrovascular and neurodegenerative diseases-a special role for pericytes","volume":"20","author":"Lendahl","year":"2019","journal-title":"EMBO Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12152"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3171\/2017.6.JNS17860"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00005.2017"},{"issue":"10","key":"B11","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a011213","article-title":"Notch signaling","volume":"4","author":"Kopan","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs019"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature25739"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.1038\/srep16449","article-title":"Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations","volume":"5","author":"Kofler","year":"2015","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10643-w"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.218271"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304849"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.10036","article-title":"Pericytes are progenitors for coronary artery smooth muscle","volume":"4","author":"Volz","year":"2015","journal-title":"Elife"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-14046"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.007512"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1242\/dev.096107"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-017-9570-9"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf030"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18497-5_6"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nature04482"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01738-3"},{"issue":"3","key":"B28","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.90905","article-title":"Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown","volume":"2","author":"Ogura","year":"2017","journal-title":"JCI Insight"},{"key":"B29","doi-asserted-by":"crossref","unstructured":"Ivanova E, Corona C, Eleftheriou CG, Bianchimano P, and Sagdullaev BT. 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