{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:59:38Z","timestamp":1792886378871,"version":"4.5.0"},"reference-count":59,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n                    Moyamoya disease (MMD) is closely associated with the Ring Finger Protein 213 ( RNF213), a susceptibility gene for MMD. However, its biological function remains unclear. We aimed to elucidate the role of RNF213 in the damage incurred by human endothelial cells under oxygen-glucose deprivation (OGD). We analyzed autophagy in peripheral blood mononuclear cells (PBMCs) derived from patients carrying either RNF213 wildtype (WT) or variant (p.R4810K). Subsequently, human umbilical vein endothelial cells (HUVECs) were transfected with RNF213 WT (HUVEC\n                    <jats:sup>WT<\/jats:sup>\n                    ) or p.R4810K (HUVEC\n                    <jats:sup>R4810K<\/jats:sup>\n                    ) and exposed to OGD for 2\u2009h. Immunoblotting was used to analyze autophagy marker proteins, and endothelial function was analyzed by tube formation assay. Autophagic vesicles were observed using transmission electron microscopy. Post-OGD exposure, we administered rapamycin and cilostazol as potential autophagy inducers. The RNF213 variant group during post-OGD exposure (vs. pre-OGD) showed autophagy inhibition, increased protein expression of SQSTM1\/p62 ( p\u2009&lt;\u20090.0001) and LC3-II ( p\u2009=\u20090.0039), and impaired endothelial function ( p\u2009=\u20090.0252). HUVEC\n                    <jats:sup>R4810K<\/jats:sup>\n                    during post-OGD exposure (versus pre-OGD) showed a remarkable increase in autophagic vesicles. Administration of rapamycin and cilostazol notably restored the function of HUVEC\n                    <jats:sup>R4810K<\/jats:sup>\n                    and autophagy. Our findings support the pivotal role of autophagy impaired by the RNF213 variant in MMD-induced endothelial cell dysfunction.\n                  <\/jats:p>","DOI":"10.1177\/0271678x241245557","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T11:59:11Z","timestamp":1712231951000},"page":"1801-1815","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["<i>RNF213<\/i>\n                    variant and autophagic impairment: A pivotal link to endothelial dysfunction in moyamoya disease"],"prefix":"10.1177","volume":"44","author":[{"given":"Hee Sun","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geun Hwa","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Sil","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Sol","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaerak","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Brain Science, Ajou University School of Medicine, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Man","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea"},{"name":"Department of Neurology, Ajou University School of Medicine, Ajou University Medical Center, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"bibr1-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70240-0"},{"key":"bibr2-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.132"},{"key":"bibr3-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1177\/1747493016662039"},{"key":"bibr4-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-019-03811-w"},{"key":"bibr5-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyy234"},{"key":"bibr6-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.52.245"},{"key":"bibr7-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.3171\/2023.7.FOCUS23327"},{"key":"bibr8-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.017701"},{"key":"bibr9-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70094-2"},{"key":"bibr10-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.09.038"},{"key":"bibr11-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-017-0950-y"},{"key":"bibr12-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.3171\/2009.1.FOCUS08310"},{"key":"bibr13-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1159\/000121249"},{"key":"bibr14-0271678X241245557","first-page":"e2254220110720","volume":"6","author":"Liu W","year":"2011","journal-title":"PLoS One"},{"key":"bibr15-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1038\/srep13191"},{"key":"bibr16-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.07.004"},{"key":"bibr17-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.006244"},{"key":"bibr18-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.001862"},{"key":"bibr19-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2014.12.006"},{"key":"bibr20-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.024712"},{"key":"bibr21-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008901"},{"key":"bibr22-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318249f71f"},{"key":"bibr23-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56185"},{"key":"bibr24-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202000807"},{"key":"bibr25-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008813"},{"key":"bibr26-0271678X241245557","first-page":"33","volume":"335","author":"Esclatine A","year":"2009","journal-title":"Curr Top Microbiol Immunol"},{"key":"bibr27-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-021-05359-z"},{"key":"bibr28-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1159\/000448301"},{"key":"bibr29-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.01.043"},{"key":"bibr30-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.4161\/auto.26336"},{"key":"bibr31-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.01.051"},{"key":"bibr32-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1702223114"},{"key":"bibr33-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.163774"},{"key":"bibr34-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000041048.33908.18"},{"key":"bibr35-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.104538"},{"key":"bibr36-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.038650"},{"key":"bibr37-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2011.0150"},{"key":"bibr38-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163561"},{"key":"bibr39-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-016-1677-5"},{"key":"bibr40-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.105305"},{"key":"bibr41-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002875"},{"key":"bibr42-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1729"},{"key":"bibr43-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.5.1485"},{"key":"bibr44-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.04.019"},{"key":"bibr45-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)93147-F"},{"key":"bibr46-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022287"},{"key":"bibr47-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.01760"},{"key":"bibr48-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02564.x"},{"key":"bibr49-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1159\/000328651"},{"key":"bibr50-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002146"},{"key":"bibr51-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03566-4"},{"key":"bibr52-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2017.03.006"},{"key":"bibr53-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1520548"},{"key":"bibr54-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15873"},{"key":"bibr55-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-014-0354-x"},{"key":"bibr56-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.527"},{"key":"bibr57-0271678X241245557","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-0923-1"},{"key":"bibr58-0271678X241245557","doi-asserted-by":"crossref","first-page":"e0134486","DOI":"10.1371\/journal.pone.0134486","volume":"10","author":"Lee HR","year":"2015","journal-title":"PLoS One"},{"key":"bibr59-0271678X241245557","doi-asserted-by":"crossref","first-page":"e0160620","DOI":"10.1371\/journal.pone.0160620","volume":"11","author":"Park SY","year":"2016","journal-title":"PLoS One"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X241245557","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X241245557","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X241245557","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:15:02Z","timestamp":1777493702000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X241245557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,4]]},"references-count":59,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1177\/0271678X241245557"],"URL":"https:\/\/doi.org\/10.1177\/0271678x241245557","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.10.11.561969","asserted-by":"object"}]},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,4]]}}}