{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:17:29Z","timestamp":1788585449801,"version":"build-2803163510"},"reference-count":40,"publisher":"Japan Atherosclerosis Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAT","J Atheroscler Thromb"],"published-print":{"date-parts":[[2026,9,1]]},"DOI":"10.5551\/jat.rv22053","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:09:28Z","timestamp":1780438168000},"page":"1124-1131","source":"Crossref","is-referenced-by-count":0,"title":["Intracranial Arterial Stenosis beyond Atherosclerosis: Insights from &lt;i&gt;RNF213&lt;\/i&gt;"],"prefix":"10.5551","volume":"33","author":[{"given":"Shuhei","family":"Okazaki","sequence":"first","affiliation":[{"name":"Department of Neurology, National Hospital Organization Osaka National Hospital"},{"name":"Department of Neurology, The University of Osaka Graduate School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3489","reference":[{"key":"1","unstructured":"1) GBD 2019 Stroke Collaborators: Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol, 2021; 20: 795-820"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Gorelick PB, Wong KS, Bae HJ, Pandey DK: Large artery intracranial occlusive disease: a large worldwide burden but a relatively neglected frontier. Stroke, 2008; 39: 2396-2399","DOI":"10.1161\/STROKEAHA.107.505776"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Mehndiratta MM, Khan M, Mehndiratta P, Wasay M: Stroke in Asia: geographical variations and temporal trends. J Neurol Neurosurg Psychiatry, 2014; 85: 1308-1312","DOI":"10.1136\/jnnp-2013-306992"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Song JY, Kwon SU: Intracranial atherosclerotic stenosis. Cerebrovasc Dis Extra, 2025; 15: 62-67","DOI":"10.1159\/000543356"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Hurford R, Wolters FJ, Li L, Lau KK, Kuker W, Rothwell PM, Oxford Vascular Study Phenotyped Cohort: Prevalence, predictors, and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke: a population-based cohort study. Lancet Neurol, 2020; 19: 413-421","DOI":"10.1016\/S1474-4422(20)30079-X"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, Janis LS, Lutsep HL, Barnwell SL, Waters MF, Hoh BL, Hourihane JM, Levy EI, Alexandrov AV, Harrigan MR, Chiu D, Klucznik RP, Clark JM, McDougall CG, Johnson MD, Pride GL, Torbey MT, Zaidat OO, Rumboldt Z, Cloft HJ: Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med, 2011; 365: 993-1003","DOI":"10.1056\/NEJMoa1105335"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Bang OY, Toyoda K, Arenillas JF, Liu L, Kim JS: Intracranial large artery disease of non-atherosclerotic origin: recent progress and clinical implications. J Stroke, 2018; 20: 208-217","DOI":"10.5853\/jos.2018.00150"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Kamada F, Aoki Y, Narisawa A, Abe Y, Komatsuzaki S, Kikuchi A, Kanno J, Niihori T, Ono M, Ishii N, Owada Y, Fujimura M, Mashimo Y, Suzuki Y, Hata A, Tsuchiya S, Tominaga T, Matsubara Y, Kure S: A genome-wide association study identifies RNF213 as the first moyamoya disease gene. J Hum Genet, 2011; 56: 34-40","DOI":"10.1038\/jhg.2010.132"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Liu W, Morito D, Takashima S, Mineharu Y, Kobayashi H, Hitomi T, Hashikata H, Matsuura N, Yamazaki S, Toyoda A, Kikuta K, Takagi Y, Harada KH, Fujiyama A, Herzig R, Krischek B, Zou L, Kim JE, Kitakaze M, Miyamoto S, Nagata K, Hashimoto N, Koizumi A: Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development. PLoS One, 2011; 6: e22542","DOI":"10.1371\/journal.pone.0022542"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Okazaki S, Morimoto T, Kamatani Y, Kamimura T, Kobayashi H, Harada K, Tomita T, Higashiyama A, Takahashi JC, Nakagawara J, Koga M, Toyoda K, Washida K, Saito S, Takahashi A, Hirata M, Matsuda K, Mochizuki H, Chong M, Pare G, O\u2019Donnell M, Ago T, Hata J, Ninomiya T, Dichgans M, Debette S, Kubo M, Koizumi A, Ihara M: Moyamoya disease susceptibility variant RNF213 p.R4810K increases the risk of ischemic stroke attributable to large-artery atherosclerosis. Circulation, 2019; 139: 295-298","DOI":"10.1161\/CIRCULATIONAHA.118.038439"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Chen XY, Wong KS, Lam WWM, Zhao HL, Ng HK: Middle cerebral artery atherosclerosis: histological comparison between plaques associated with and not associated with infarct in a postmortem study. Cerebrovasc Dis, 2008; 25: 74-80","DOI":"10.1159\/000111525"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Dieleman N, van der Kolk AG, Zwanenburg JJM, Harteveld AA, Biessels GJ, Luijten PR, Hendrikse J: Imaging intracranial vessel wall pathology with magnetic resonance imaging: current prospects and future directions. Circulation, 2014; 130: 192-201","DOI":"10.1161\/CIRCULATIONAHA.113.006919"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) van der Kolk AG, Zwanenburg JJM, Denswil NP, Vink A, Spliet WGM, Daemen MJAP, Visser F, Klomp DWJ, Luijten PR, Hendrikse J: Imaging the intracranial atherosclerotic vessel wall using 7T MRI: initial comparison with histopathology. AJNR Am J Neuroradiol, 2015; 36: 694-701","DOI":"10.3174\/ajnr.A4178"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC, Turan TN, Williams LS: 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association\/American Stroke Association. Stroke, 2021; 52: e364-e467","DOI":"10.1161\/STR.0000000000000375"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Miyamoto S, Ogasawara K, Kuroda S, Itabashi R, Toyoda K, Itoh Y, Iguchi Y, Shiokawa Y, Takagi Y, Ohtsuki T, Kinouchi H, Okada Y, Takahashi JC, Nakase H, Kakuda W, Committee for Stroke Guideline 2021, the Japan Stroke Society: Japan Stroke Society guideline 2021 for the treatment of stroke. Int J Stroke, 2022; 17: 1039-1049","DOI":"10.1177\/17474930221090347"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Debette S, Compter A, Labeyrie MA, Uyttenboogaart M, Metso TM, Majersik JJ, Goeggel-Simonetti B, Engelter ST, Pezzini A, Bijlenga P, Southerland AM, Naggara O, Bejot Y, Cole JW, Ducros A, Giacalone G, Schilling S, Reiner P, Sarikaya H, Welleweerd JC, Kappelle LJ, de Borst GJ, Bonati LH, Jung S, Thijs V, Martin JJ, Brandt T, Grond-Ginsbach C, Kloss M, Mizutani T, Minematsu K, Meschia JF, Pereira VM, Bersano A, Touze E, Lyrer PA, Leys D, Chabriat H, Markus HS, Worrall BB, Chabrier S, Baumgartner R, Stapf C, Tatlisumak T, Arnold M, Bousser MG: Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection. Lancet Neurol, 2015; 14: 640-654","DOI":"10.1016\/S1474-4422(15)00009-5"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Salvarani C, Hunder GG, Brown RD: Primary central nervous system vasculitis. N Engl J Med, 2024; 391: 1028-1037","DOI":"10.1056\/NEJMra2314942"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Ducros A: Reversible cerebral vasoconstriction syndrome. Lancet Neurol, 2012; 11: 906-917","DOI":"10.1016\/S1474-4422(12)70135-7"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Ihara M, Yamamoto Y, Hattori Y, Liu W, Kobayashi H, Ishiyama H, Yoshimoto T, Miyawaki S, Clausen T, Bang OY, Steinberg GK, Tournier-Lasserve E, Koizumi A: Moyamoya disease: diagnosis and interventions. Lancet Neurol, 2022; 21: 747-758","DOI":"10.1016\/S1474-4422(22)00165-X"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Mandell DM, Mossa-Basha M, Qiao Y, Hess CP, Hui F, Matouk C, Johnson MH, Daemen MJAP, Vossough A, Edjlali M, Saloner D, Ansari SA, Wasserman BA, Mikulis DJ, Vessel Wall Imaging Study Group of the American Society of Neuroradiology: Intracranial vessel wall MRI: principles and expert consensus recommendations of the American Society of Neuroradiology. AJNR Am J Neuroradiol, 2017; 38: 218-229","DOI":"10.3174\/ajnr.A4893"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Alexander MD, Yuan C, Rutman A, Tirschwell DL, Palagallo G, Gandhi D, Sekhar LN, Mossa-Basha M: High-resolution intracranial vessel wall imaging: imaging beyond the lumen. J Neurol Neurosurg Psychiatry, 2016; 87: 589-597","DOI":"10.1136\/jnnp-2015-312020"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Miyawaki S, Imai H, Takayanagi S, Mukasa A, Nakatomi H, Saito N: Identification of a genetic variant common to moyamoya disease and intracranial major artery stenosis\/occlusion. Stroke, 2012; 43: 3371-3374","DOI":"10.1161\/STROKEAHA.112.663864"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Kamimura T, Okazaki S, Morimoto T, Kobayashi H, Harada K, Tomita T, Higashiyama A, Yoshimoto T, Takahashi JC, Nakagawara J, Koga M, Toyoda K, Maruyama H, Koizumi A, Ihara M: Prevalence of RNF213 p.R4810K variant in early-onset stroke with intracranial arterial stenosis. Stroke, 2019; 50: 1561-1563","DOI":"10.1161\/STROKEAHA.118.024712"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Okazaki S, Yoshimoto T, Ohara M, Takagaki M, Nakamura H, Watanabe K, Gon Y, Todo K, Sasaki T, Araki H, Yamada T, Manabe S, Kishima H, Ihara M, Mochizuki H: Effect of the RNF213 p.R4810K variant on the progression of intracranial artery stenosis: a 15-year follow-up study. Neurol Genet, 2022; 8: e200029","DOI":"10.1212\/NXG.0000000000200029"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Dofuku S, Miyawaki S, Imai H, Shimizu M, Hongo H, Shinya Y, Ohara K, Teranishi Y, Ono H, Nakatomi H, Teraoka A, Saito N: RNF213 p.Arg4810Lys variant is associated with higher stenosis progression in asymptomatic intracranial artery stenosis. Transl Stroke Res, 2025; 16: 1293-1300","DOI":"10.1007\/s12975-024-01309-x"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Dofuku S, Sonehara K, Miyawaki S, Sakaue S, Imai H, Shimizu M, Hongo H, Shinya Y, Ohara K, Teranishi Y, Okano A, Ono H, Nakatomi H, Teraoka A, Yamamoto K, Maeda Y, Nii T, Kishikawa T, Suzuki K, Hirata J, Takahashi M, Matsuda K, Kumanogoh A, Matsuda F, Okada Y, Saito N: Genome-wide association study of intracranial artery stenosis followed by phenome-wide association study. Transl Stroke Res, 2023; 14: 322-333","DOI":"10.1007\/s12975-022-01049-w"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Zedde M, Grisendi I, Assenza F, Napoli M, Moratti C, Pavone C, Bonacini L, Di Cecco G, D\u2019Aniello S, Stoenoiu MS, Persu A, Valzania F, Pascarella R: RNF213 polymorphisms in intracranial artery dissection. Genes (Basel), 2024; 15: 725","DOI":"10.3390\/genes15060725"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Yoshimoto T, Ishiyama H, Hattori Y, Nishimura K, Okada Y, Watanabe H, Ohyagi Y, Akaiwa Y, Miyamoto T, Kawamoto M, Ichijo M, Inoue H, Matsukawa N, Mizuno T, Matsuyama H, Tomimoto H, Kawakami D, Toyoda K, Koga M, Ihara M: Association of thyroid peroxidase antibody with the RNF213 p.R4810K variant in ischemic stroke\/transient ischemic attack. Atherosclerosis, 2023; 382: 117281","DOI":"10.1016\/j.atherosclerosis.2023.117281"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Morimoto T, Mineharu Y, Kobayashi H, Harada KH, Funaki T, Takagi Y, Sakai N, Miyamoto S, Koizumi A: Significant association of the RNF213 p.R4810K polymorphism with quasi-moyamoya disease. J Stroke Cerebrovasc Dis, 2016; 25: 2632-2636","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.07.004"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Chang SA, Song JS, Park TK, Yang JH, Kwon WC, Kim SR, Kim SM, Cha J, Jang SY, Cho YS, Kim TJ, Bang OY, Song JY, Ki CS, Kim DK: Nonsyndromic peripheral pulmonary artery stenosis is associated with homozygosity of RNF213 p.Arg4810Lys regardless of co-occurrence of moyamoya disease. Chest, 2018; 153: 404-413","DOI":"10.1016\/j.chest.2017.09.023"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Ishiyama H, Tanaka T, Yoshimoto T, Takahashi A, Ogata S, Nishimura K, Asano Y, Koizumi A, Noguchi T, Ihara M: RNF213 p.R4810K variant increases the risk of vasospastic angina. JACC Asia, 2023; 3: 821-823","DOI":"10.1016\/j.jacasi.2023.05.002"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Hikino K, Koyama S, Ito K, Koike Y, Koido M, Matsumura T, Kurosawa R, Tomizuka K, Ito S, Liu X, Ishikawa Y, Momozawa Y, Morisaki T, Kamatani Y, Mushiroda T, Terao C, Biobank Japan Project: RNF213 variants, vasospastic angina, and risk of fatal myocardial infarction. JAMA Cardiol, 2024; 9: 723-731","DOI":"10.1001\/jamacardio.2024.1483"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Suzuki H, Kataoka M, Hiraide T, Aimi Y, Yamada Y, Katsumata Y, Chiba T, Kanekura K, Isobe S, Sato Y, Satoh T, Gamou S, Fukuda K, Kosaki K: Genomic comparison with supercentenarians identifies RNF213 as a risk gene for pulmonary arterial hypertension. Circ Genom Precis Med, 2018; 11: e002317","DOI":"10.1161\/CIRCGEN.118.002317"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Hiraide T, Kataoka M, Suzuki H, Aimi Y, Chiba T, Isobe S, Katsumata Y, Goto S, Kanekura K, Yamada Y, Moriyama H, Kitakata H, Endo J, Yuasa S, Arai Y, Hirose N, Satoh T, Hakamata Y, Sano M, Gamou S, Kosaki K, Fukuda K: Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension. J Heart Lung Transplant, 2020; 39: 103-112","DOI":"10.1016\/j.healun.2019.08.022"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Roy V, Ross JP, Pepin R, Cortez Ghio S, Brodeur A, Touzel Deschenes L, Le-Bel G, Phillips DE, Milot G, Dion PA, Guerin S, Germain L, Berthod F, Auger FA, Rouleau GA, Dupre N, Gros-Louis F: Moyamoya disease susceptibility gene RNF213 regulates endothelial barrier function. Stroke, 2022; 53: 1263-1275","DOI":"10.1161\/STROKEAHA.120.032691"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Kobayashi H, Matsuda Y, Hitomi T, Okuda H, Shioi H, Matsuda T, Imai H, Sone M, Taura D, Harada KH, Habu T, Takagi Y, Miyamoto S, Koizumi A: Biochemical and functional characterization of RNF213 (mysterin) R4810K, a susceptibility mutation of moyamoya disease, in angiogenesis in vitro and in vivo. J Am Heart Assoc, 2015; 4: 1-19","DOI":"10.1161\/JAHA.115.002146"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Sugihara M, Morito D, Ainuki S, Hirano Y, Ogino K, Kitamura A, Hirata H, Nagata K: The AAA+ ATPase\/ubiquitin ligase mysterin stabilizes cytoplasmic lipid droplets. J Cell Biol, 2019; 218: 949-960","DOI":"10.1083\/jcb.201712120"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Walsh SC, Reitano JR, Dickinson MS, Kutsch M, Hernandez D, Barnes AB, Schott BH, Wang L, Ko DC, Kim SY, Valdivia RH, Bastidas RJ, Coers J: The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction. Cell Host Microbe, 2022; 30: 1671-1684.e9","DOI":"10.1016\/j.chom.2022.08.008"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Zhou X, Zhang H, Wang Y, Wang D, Lin Z, Zhang Y, Tang Y, Liu J, Yao YF, Zhang Y, Pan L: Shigella effector IpaH1.4 subverts host E3 ligase RNF213 to evade antibacterial immunity. Nat Commun, 2025; 16: 3099","DOI":"10.1038\/s41467-025-58432-y"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Hoshino H, Izawa Y, Suzuki N, Research Committee on Moyamoya Disease: Epidemiological features of moyamoya disease in Japan. Neurol Med Chir (Tokyo), 2012; 52: 295-298","DOI":"10.2176\/nmc.52.295"}],"container-title":["Journal of Atherosclerosis and Thrombosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jat\/33\/9\/33_RV22053\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:52:19Z","timestamp":1788583939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jat\/33\/9\/33_RV22053\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":40,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.5551\/jat.rv22053","relation":{},"ISSN":["1340-3478","1880-3873"],"issn-type":[{"value":"1340-3478","type":"print"},{"value":"1880-3873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"article-number":"RV22053"}}