{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:59:42Z","timestamp":1792886382014,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RRC 2018-2026"],"award-info":[{"award-number":["RRC 2018-2026"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RF-2019-12369247"],"award-info":[{"award-number":["RF-2019-12369247"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RCR-2021-23671214"],"award-info":[{"award-number":["RCR-2021-23671214"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["PNRR-MR1-2022-12376618"],"award-info":[{"award-number":["PNRR-MR1-2022-12376618"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PNRR-MR1-2022-12376618"],"award-info":[{"award-number":["PNRR-MR1-2022-12376618"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: The pathophysiological mechanisms of Moyamoya angiopathy (MA) are still largely unknown, although a dysfunctional vasculogenesis has been hypothesized to contribute to it. The association between this rare cerebrovascular condition and variants of Ring Finger Protein 213 (RNF213) strengthens the role of genetic factors in MA pathogenesis. Methods: To investigate the molecular mechanisms of MA, we carried out RNA interference (RNAi) targeting RNF213 in human endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). The combined effect of RNAi and\/or hypoxia on expression of key angiogenic factors was analyzed through qRT-PCR and Western blot. Functional assays were performed to characterize the impact of RNAi on vasculogenesis. Gene-expression arrays were performed on vessel walls of MA patients and controls. Results: RNF213-RNAi impaired angiogenic capability in ECs, whereas the simultaneous silencing of RNF213 and its phosphatase PTP1B restored angiogenesis function in ECs but worsened it in VSMCs. Angiogenic factor expression appeared to be modulated in ECs by the combined effects of RNAi and\/or hypoxia, and in pathological vessels of MA patients as compared with controls. Conclusions: Our findings contribute to associating the relevance of RNF213 in MA cellular models and highlight the importance of EC-VSMC crosstalk for vascular integrity. Additionally, the study could lay the foundations for improving experimental models of MA pathophysiology.<\/jats:p>","DOI":"10.3390\/cells15100862","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:42:18Z","timestamp":1779691338000},"page":"862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Experimental Approach to Moyamoya Angiopathy: Insights into Vascular Cell Crosstalk"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8483-3509","authenticated-orcid":false,"given":"Gemma","family":"Gorla","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6811-6112","authenticated-orcid":false,"given":"Antonella","family":"Potenza","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"},{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-1374","authenticated-orcid":false,"given":"Tatiana","family":"Carrozzini","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0256-9706","authenticated-orcid":false,"given":"Giuliana","family":"Pollaci","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"},{"name":"Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Pasella","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2724-2291","authenticated-orcid":false,"given":"Erika","family":"Salvi","sequence":"additional","affiliation":[{"name":"Data Science Center and Computational Multi-Omics of Neurological Disorders (MIND) Lab, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"},{"name":"Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0141-0437","authenticated-orcid":false,"given":"Isabella","family":"Canavero","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0423-8759","authenticated-orcid":false,"given":"Nicola","family":"Rifino","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Ferroli","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5494-8292","authenticated-orcid":false,"given":"Marco Paolo","family":"Schiariti","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Restelli","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Acerbi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"},{"name":"Unit of Neurosurgery, University Hospital of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-628X","authenticated-orcid":false,"given":"Anna","family":"Bersano","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-5031","authenticated-orcid":false,"given":"Laura","family":"Gatti","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5853\/jos.2015.01627","article-title":"Moyamoya Disease: Epidemiology, Clinical Features, and Diagnosis","volume":"18","author":"Kim","year":"2016","journal-title":"J. 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