{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:21:01Z","timestamp":1792977661895,"version":"4.5.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["RS-2022-NR069269"],"award-info":[{"award-number":["RS-2022-NR069269"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["2019R1A2C209009911"],"award-info":[{"award-number":["2019R1A2C209009911"]}]},{"name":"SNUH Research Fund by the Seoul National University Hospital","award":["03-20190080"],"award-info":[{"award-number":["03-20190080"]}]},{"name":"SNUH Kun-hee Lee Child Cancer & Rare Disease Project, Republic of Korea","award":["23C-027-0100"],"award-info":[{"award-number":["23C-027-0100"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Moyamoya disease (MMD) is a chronic cerebrovascular disorder and a leading cause of pediatric stroke. Extracellular vesicles (EVs) carrying microRNAs (miRNAs) play a pivotal role in intercellular communication within cerebrovascular diseases. This study aimed to identify specific miRNAs within plasma-derived EVs from MMD patients and investigate their functional implications. Study subjects included healthy controls (<jats:italic>N<\/jats:italic>\u2009=\u200913) and MMD patients (<jats:italic>N<\/jats:italic>\u2009=\u200923). EVs were isolated from plasma samples and characterized by transmission electron microscopy, nanoparticle tracking analysis, ExoView, RT-qPCR, and immunoblotting. miRNA profiles were assessed through NanoString analysis. Functional effects of miR-512-3p inhibition were evaluated in MMD endothelial colony-forming cells (ECFCs) by analyzing guanosine triphosphatase (GTPase) activity, tubule formation, and cell viability. MMD-derived EVs exhibited an upregulation of miR-512-3p compared to controls. Bioinformatics analysis identified RHO guanine nucleotide exchange factor 3 (ARHGEF3) as a potential target of miR-512-3p. Inhibition of miR-512-3p in MMD ECFCs resulted in increased expression of ARHGEF3 and its downstream effector RHOA, leading to enhanced GTPase activity and improved tubule formation, indicative of restored angiogenic function. Elevated levels of miR-512-3p within plasma-derived EVs may serve as a novel biomarker for MMD diagnosis. The modulation of ARHGEF3 and subsequent RHOA signaling by targeting miR-512-3p contributes to the dysregulated angiogenesis in MMD.<\/jats:p>","DOI":"10.1038\/s41598-025-08796-4","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T08:46:48Z","timestamp":1752137208000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Plasma extracellular vesicle-associated miR-512-3p modulates angiogenesis in pediatric Moyamoya disease by targeting ARHGEF3."],"prefix":"10.1038","volume":"15","author":[{"given":"Eun Jung","family":"Koh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Ah","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn Joo","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heeyoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hoon","family":"Phi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ki","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"8796_CR1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1159\/000442298","volume":"41","author":"A Bersano","year":"2016","unstructured":"Bersano, A. et al. Research progresses in Understanding the pathophysiology of Moyamoya disease. Cerebrovasc. Dis. 41, 105\u2013118. https:\/\/doi.org\/10.1159\/000442298 (2016).","journal-title":"Cerebrovasc. Dis."},{"key":"8796_CR2","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.pediatrneurol.2016.06.012","volume":"63","author":"AJ Ball","year":"2016","unstructured":"Ball, A. J., Steinberg, G. K. & Elbers, J. Quality of life in pediatric Moyamoya disease. Pediatr. Neurol. 63, 60\u201365. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2016.06.012 (2016).","journal-title":"Pediatr. Neurol."},{"key":"8796_CR3","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1054\/jocn.1999.0160","volume":"7","author":"N Saeki","year":"2000","unstructured":"Saeki, N. et al. Comparative performance of magnetic resonance angiography and conventional angiography in Moyamoya disease. J. Clin. Neurosci. 7, 112\u2013115. https:\/\/doi.org\/10.1054\/jocn.1999.0160 (2000).","journal-title":"J. Clin. Neurosci."},{"key":"8796_CR4","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.pediatrneurol.2018.10.006","volume":"91","author":"N Dlamini","year":"2019","unstructured":"Dlamini, N., Muthusami, P. & Amlie-Lefond, C. Childhood moyamoya: looking back to the future. Pediatr. Neurol. 91, 11\u201319. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2018.10.006 (2019).","journal-title":"Pediatr. Neurol."},{"key":"8796_CR5","doi-asserted-by":"publisher","unstructured":"Santiago-Hernandez, A. et al. Metabolic alterations identified in urine, plasma and aortic smooth muscle cells reflect cardiovascular risk in patients with programmed coronary artery bypass grafting. Antioxid. (Basel). 10 https:\/\/doi.org\/10.3390\/antiox10091369 (2021).","DOI":"10.3390\/antiox10091369"},{"key":"8796_CR6","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/978-3-030-31206-0_11","volume":"1201","author":"DM Smadja","year":"2019","unstructured":"Smadja, D. M. Vasculogenic stem and progenitor cells in human: future cell therapy product or liquid biopsy for vascular disease. Adv. Exp. Med. Biol. 1201, 215\u2013237. https:\/\/doi.org\/10.1007\/978-3-030-31206-0_11 (2019).","journal-title":"Adv. Exp. Med. Biol."},{"key":"8796_CR7","doi-asserted-by":"publisher","unstructured":"Lee, M. J. et al. The impact of Moyamoya disease and RNF213 mutations on the spectrum of plasma protein and MicroRNA. J. Clin. Med. 8 https:\/\/doi.org\/10.3390\/jcm8101648 (2019).","DOI":"10.3390\/jcm8101648"},{"key":"8796_CR8","doi-asserted-by":"publisher","first-page":"537","DOI":"10.2174\/138920210793175895","volume":"11","author":"LA Macfarlane","year":"2010","unstructured":"Macfarlane, L. A. & Murphy, P. R. MicroRNA: biogenesis, function and role in Cancer. Curr. Genomics. 11, 537\u2013561. https:\/\/doi.org\/10.2174\/138920210793175895 (2010).","journal-title":"Curr. Genomics"},{"key":"8796_CR9","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1186\/s12935-020-01645-6","volume":"20","author":"SA Choi","year":"2020","unstructured":"Choi, S. A. et al. Extracellular vesicle-associated miR-135b and \u2013\u2009135a regulate stemness in group 4 Medulloblastoma cells by targeting angiomotin-like 2. Cancer Cell. Int. 20, 558. https:\/\/doi.org\/10.1186\/s12935-020-01645-6 (2020).","journal-title":"Cancer Cell. Int."},{"key":"8796_CR10","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.cmet.2019.07.011","volume":"30","author":"MA Mori","year":"2019","unstructured":"Mori, M. A., Ludwig, R. G., Garcia-Martin, R., Brandao, B. B. & Kahn, C. R. Extracellular mirnas: from biomarkers to mediators of physiology and disease. Cell. Metab. 30, 656\u2013673. https:\/\/doi.org\/10.1016\/j.cmet.2019.07.011 (2019).","journal-title":"Cell. Metab."},{"key":"8796_CR11","doi-asserted-by":"publisher","first-page":"e12090","DOI":"10.1002\/jev2.12090","volume":"10","author":"Y Liang","year":"2021","unstructured":"Liang, Y., Lehrich, B. M., Zheng, S. & Lu, M. Emerging methods in biomarker identification for extracellular vesicle-based liquid biopsy. J. Extracell. Vesicles. 10, e12090. https:\/\/doi.org\/10.1002\/jev2.12090 (2021).","journal-title":"J. Extracell. Vesicles"},{"key":"8796_CR12","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/ncb1596","volume":"9","author":"H Valadi","year":"2007","unstructured":"Valadi, H. et al. Exosome-mediated transfer of mRNAs and MicroRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell. Biol. 9, 654\u2013659. https:\/\/doi.org\/10.1038\/ncb1596 (2007).","journal-title":"Nat. Cell. Biol."},{"key":"8796_CR13","doi-asserted-by":"publisher","unstructured":"Cheng, L., Sharples, R. A., Scicluna, B. J. & Hill, A. F. Exosomes provide a protective and enriched source of MiRNA for biomarker profiling compared to intracellular and cell-free blood. J. Extracell. Vesicles. 3 https:\/\/doi.org\/10.3402\/jev.v3.23743 (2014).","DOI":"10.3402\/jev.v3.23743"},{"key":"8796_CR14","doi-asserted-by":"publisher","unstructured":"Kim, K. M., Abdelmohsen, K., Mustapic, M., Kapogiannis, D. & Gorospe M. RNA in extracellular vesicles. Wiley Interdiscip Rev. RNA. 8 https:\/\/doi.org\/10.1002\/wrna.1413 (2017).","DOI":"10.1002\/wrna.1413"},{"key":"8796_CR15","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s00381-019-04099-y","volume":"35","author":"A Jangra","year":"2019","unstructured":"Jangra, A. et al. Panobinostat, a histone deacetylase inhibitor, rescues the angiogenic potential of endothelial colony-forming cells in Moyamoya disease. Childs Nerv. Syst. 35, 823\u2013831. https:\/\/doi.org\/10.1007\/s00381-019-04099-y (2019).","journal-title":"Childs Nerv. Syst."},{"key":"8796_CR16","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1161\/ATVBAHA.115.305363","volume":"35","author":"JY Lee","year":"2015","unstructured":"Lee, J. Y. et al. Deregulation of retinaldehyde dehydrogenase 2 leads to defective angiogenic function of endothelial Colony-Forming cells in pediatric Moyamoya disease. Arterioscler. Thromb. Vasc Biol. 35, 1670\u20131677. https:\/\/doi.org\/10.1161\/ATVBAHA.115.305363 (2015).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"8796_CR17","doi-asserted-by":"publisher","first-page":"e0183640","DOI":"10.1371\/journal.pone.0183640","volume":"12","author":"SJ Kuravi","year":"2017","unstructured":"Kuravi, S. J. et al. Changes in the pattern of plasma extracellular vesicles after severe trauma. PLoS One. 12, e0183640. https:\/\/doi.org\/10.1371\/journal.pone.0183640 (2017).","journal-title":"PLoS One"},{"key":"8796_CR18","doi-asserted-by":"publisher","unstructured":"Agarwal, V., Bell, G. W., Nam, J. W. & Bartel, D. P. Predicting effective MicroRNA target sites in mammalian mRNAs. Elife 4 https:\/\/doi.org\/10.7554\/eLife.05005 (2015).","DOI":"10.7554\/eLife.05005"},{"key":"8796_CR19","doi-asserted-by":"publisher","unstructured":"McGeary, S. E. et al. The biochemical basis of MicroRNA targeting efficacy. Science 366 https:\/\/doi.org\/10.1126\/science.aav1741 (2019).","DOI":"10.1126\/science.aav1741"},{"key":"8796_CR20","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1002\/pmic.201400515","volume":"15","author":"M Pathan","year":"2015","unstructured":"Pathan, M. et al. FunRich: an open access standalone functional enrichment and interaction network analysis tool. Proteomics 15, 2597\u20132601. https:\/\/doi.org\/10.1002\/pmic.201400515 (2015).","journal-title":"Proteomics"},{"key":"8796_CR21","doi-asserted-by":"publisher","first-page":"D587","DOI":"10.1093\/nar\/gkac963","volume":"51","author":"M Kanehisa","year":"2023","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 51, D587\u2013d592. https:\/\/doi.org\/10.1093\/nar\/gkac963 (2023).","journal-title":"Nucleic Acids Res."},{"key":"8796_CR22","doi-asserted-by":"publisher","first-page":"D679","DOI":"10.1093\/nar\/gkad960","volume":"52","author":"A Agrawal","year":"2023","unstructured":"Agrawal, A. et al. WikiPathways 2024: next generation pathway database. Nucleic Acids Res. 52, D679\u2013D689. https:\/\/doi.org\/10.1093\/nar\/gkad960 (2023).","journal-title":"Nucleic Acids Res."},{"key":"8796_CR23","doi-asserted-by":"publisher","first-page":"26913","DOI":"10.3402\/jev.v3.26913","volume":"3","author":"J Lotvall","year":"2014","unstructured":"Lotvall, J. et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the international society for extracellular vesicles. J. Extracell. Vesicles. 3, 26913. https:\/\/doi.org\/10.3402\/jev.v3.26913 (2014).","journal-title":"J. Extracell. Vesicles"},{"key":"8796_CR24","first-page":"1147","volume":"15","author":"L Zhao","year":"2006","unstructured":"Zhao, L. et al. The effect of RhoA on human umbilical vein endothelial cell migration and angiogenesis in vitro. Oncol. Rep. 15, 1147\u20131152 (2006).","journal-title":"Oncol. Rep."},{"key":"8796_CR25","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1161\/01.atv.0000054198.68894.88","volume":"23","author":"GP van Nieuw Amerongen","year":"2003","unstructured":"van Nieuw Amerongen, G. P., Koolwijk, P., Versteilen, A. & van Hinsbergh, V. W. Involvement of rhoa\/rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro. Arterioscler. Thromb. Vasc Biol. 23, 211\u2013217. https:\/\/doi.org\/10.1161\/01.atv.0000054198.68894.88 (2003).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"8796_CR26","doi-asserted-by":"publisher","first-page":"5000","DOI":"10.1039\/c2lc40389g","volume":"12","author":"JW Song","year":"2012","unstructured":"Song, J. W., Daubriac, J., Tse, J. M., Bazou, D. & Munn, L. L. RhoA mediates flow-induced endothelial sprouting in a 3-D tissue analogue of angiogenesis. Lab. Chip. 12, 5000\u20135006. https:\/\/doi.org\/10.1039\/c2lc40389g (2012).","journal-title":"Lab. Chip"},{"key":"8796_CR27","doi-asserted-by":"publisher","first-page":"577688","DOI":"10.1016\/j.jneuroim.2021.577688","volume":"359","author":"L Liao","year":"2021","unstructured":"Liao, L. et al. Disrupting RhoA activity by blocking Arhgef3 expression mitigates microglia-induced neuroinflammation post spinal cord contusion. J. Neuroimmunol. 359, 577688. https:\/\/doi.org\/10.1016\/j.jneuroim.2021.577688 (2021).","journal-title":"J. Neuroimmunol."},{"key":"8796_CR28","doi-asserted-by":"publisher","first-page":"25836","DOI":"10.18632\/oncotarget.8283","volume":"7","author":"TH Liu","year":"2016","unstructured":"Liu, T. H. et al. The putative tumor activator ARHGEF3 promotes nasopharyngeal carcinoma cell pathogenesis by inhibiting cellular apoptosis. Oncotarget 7, 25836\u201325848. https:\/\/doi.org\/10.18632\/oncotarget.8283 (2016).","journal-title":"Oncotarget"},{"key":"8796_CR29","doi-asserted-by":"publisher","first-page":"806258","DOI":"10.3389\/fcell.2021.806258","volume":"9","author":"SA Khaliq","year":"2021","unstructured":"Khaliq, S. A., Umair, Z. & Yoon, M. S. Role of ARHGEF3 as a GEF and mTORC2 regulator. Front. Cell. Dev. Biol. 9, 806258. https:\/\/doi.org\/10.3389\/fcell.2021.806258 (2021).","journal-title":"Front. Cell. Dev. Biol."},{"key":"8796_CR30","doi-asserted-by":"publisher","first-page":"e0147758","DOI":"10.1371\/journal.pone.0147758","volume":"11","author":"PR Norden","year":"2016","unstructured":"Norden, P. R., Kim, D. J., Barry, D. M., Cleaver, O. B. & Davis, G. E. Cdc42 and k-Ras control endothelial tubulogenesis through apical membrane and cytoskeletal polarization: novel stimulatory roles for GTPase effectors, the small gtpases, Rac2 and Rap1b, and inhibitory influence of Arhgap31 and Rasa1. PLoS One. 11, e0147758. https:\/\/doi.org\/10.1371\/journal.pone.0147758 (2016).","journal-title":"PLoS One"},{"key":"8796_CR31","doi-asserted-by":"publisher","unstructured":"El Atat, O., Fakih, A. & El-Sibai, M. R. H. O. G. Activates RAC1 through CDC42 leading to tube formation in vascular endothelial cells. Cells 8 https:\/\/doi.org\/10.3390\/cells8020171 (2019).","DOI":"10.3390\/cells8020171"},{"key":"8796_CR32","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1007\/s00018-007-7008-z","volume":"64","author":"BA Bryan","year":"2007","unstructured":"Bryan, B. A. & D\u2019Amore, P. A. What tangled webs they weave: Rho-GTPase control of angiogenesis. Cell. Mol. Life Sci. 64, 2053\u20132065. https:\/\/doi.org\/10.1007\/s00018-007-7008-z (2007).","journal-title":"Cell. Mol. Life Sci."},{"key":"8796_CR33","doi-asserted-by":"publisher","unstructured":"Barlow, H. R. & Cleaver, O. Building blood Vessels-One Rho GTPase at a time. Cells 8 https:\/\/doi.org\/10.3390\/cells8060545 (2019).","DOI":"10.3390\/cells8060545"},{"key":"8796_CR34","doi-asserted-by":"publisher","first-page":"11666","DOI":"10.1038\/s41598-019-48053-z","volume":"9","author":"FT Zahra","year":"2019","unstructured":"Zahra, F. T. et al. Endothelial RhoA GTPase is essential for in vitro endothelial functions but dispensable for physiological in vivo angiogenesis. Sci. Rep. 9, 11666. https:\/\/doi.org\/10.1038\/s41598-019-48053-z (2019).","journal-title":"Sci. Rep."},{"key":"8796_CR35","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1158\/1940-6207.Capr-23-0156","volume":"17","author":"S Alimena","year":"2024","unstructured":"Alimena, S. et al. Differences in serum MiRNA profiles by race, ethnicity, and socioeconomic status: implications for developing an equitable ovarian Cancer screening test. Cancer Prev. Res. (Phila). 17, 177\u2013185. https:\/\/doi.org\/10.1158\/1940-6207.Capr-23-0156 (2024).","journal-title":"Cancer Prev. Res. (Phila)"},{"key":"8796_CR36","doi-asserted-by":"publisher","first-page":"725","DOI":"10.18632\/aging.100603","volume":"5","author":"N Noren Hooten","year":"2013","unstructured":"Noren Hooten, N. et al. Age-related changes in MicroRNA levels in serum. Aging (Albany NY). 5, 725\u2013740. https:\/\/doi.org\/10.18632\/aging.100603 (2013).","journal-title":"Aging (Albany NY)"},{"key":"8796_CR37","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1515\/cclm-2024-0531","volume":"62","author":"M Sopi\u0107","year":"2024","unstructured":"Sopi\u0107, M., Devaux, Y. & de Gonzalo-Calvo, D. Navigating the path of reproducibility in microRNA-based biomarker research with ring trials. Clin. Chem. Lab. Med. 62, 2393\u20132397. https:\/\/doi.org\/10.1515\/cclm-2024-0531 (2024).","journal-title":"Clin. Chem. Lab. Med."},{"key":"8796_CR38","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1515\/cclm-2016-0471","volume":"55","author":"J Khan","year":"2017","unstructured":"Khan, J., Lieberman, J. A. & Lockwood, C. M. Variability in, variability out: best practice recommendations to standardize pre-analytical variables in the detection of Circulating and tissue MicroRNAs. Clin. Chem. Lab. Med. 55, 608\u2013621. https:\/\/doi.org\/10.1515\/cclm-2016-0471 (2017).","journal-title":"Clin. Chem. Lab. Med."},{"key":"8796_CR39","doi-asserted-by":"publisher","first-page":"020501","DOI":"10.11613\/bm.2024.020501","volume":"34","author":"M Zendjabil","year":"2024","unstructured":"Zendjabil, M. Preanalytical, analytical and postanalytical considerations in Circulating MicroRNAs measurement. Biochem. Med. (Zagreb). 34, 020501. https:\/\/doi.org\/10.11613\/bm.2024.020501 (2024).","journal-title":"Biochem. Med. (Zagreb)"},{"key":"8796_CR40","doi-asserted-by":"publisher","first-page":"548278","DOI":"10.3389\/fnins.2020.548278","volume":"14","author":"G Wang","year":"2020","unstructured":"Wang, G. et al. A panel of Exosome-Derived MiRNAs of cerebrospinal fluid for the diagnosis of Moyamoya disease. Front. Neurosci. 14, 548278. https:\/\/doi.org\/10.3389\/fnins.2020.548278 (2020).","journal-title":"Front. Neurosci."},{"key":"8796_CR41","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1007\/s00701-023-05579-6","volume":"165","author":"S Ota","year":"2023","unstructured":"Ota, S. et al. Moyamoya disease-specific extracellular vesicle-derived MicroRNAs in the cerebrospinal fluid revealed by comprehensive expression analysis through MicroRNA sequencing. Acta Neurochir. 165, 2045\u20132055. https:\/\/doi.org\/10.1007\/s00701-023-05579-6 (2023).","journal-title":"Acta Neurochir."},{"key":"8796_CR42","doi-asserted-by":"publisher","first-page":"100247","DOI":"10.1016\/j.clinsp.2023.100247","volume":"78","author":"D Huang","year":"2023","unstructured":"Huang, D., Qi, H., Yang, H. & Chen, M. Plasma Exosomal MicroRNAs are non-invasive biomarkers of Moyamoya disease: A pilot study. Clinics 78, 100247. https:\/\/doi.org\/10.1016\/j.clinsp.2023.100247 (2023).","journal-title":"Clinics"},{"key":"8796_CR43","doi-asserted-by":"publisher","unstructured":"Wang, M. et al. Exosomal micrornas: biomarkers of Moyamoya disease and involvement in vascular cytoskeleton reconstruction. Heliyon 10 https:\/\/doi.org\/10.1016\/j.heliyon.2024.e32022 (2024).","DOI":"10.1016\/j.heliyon.2024.e32022"},{"key":"8796_CR44","doi-asserted-by":"publisher","unstructured":"Liu, J. et al. Plasma-derived exosomes contributes to endothelial-to-mesenchymal transition in Moyamoya disease. Heliyon 10 https:\/\/doi.org\/10.1016\/j.heliyon.2024.e26748 (2024).","DOI":"10.1016\/j.heliyon.2024.e26748"},{"key":"8796_CR45","doi-asserted-by":"publisher","first-page":"42964","DOI":"10.1074\/jbc.M207401200","volume":"277","author":"WT Arthur","year":"2002","unstructured":"Arthur, W. T., Ellerbroek, S. M., Der, C. J., Burridge, K. & Wennerberg, K. XPLN, a guanine nucleotide exchange factor for RhoA and rhob, but not RhoC. J. Biol. Chem. 277, 42964\u201342972. https:\/\/doi.org\/10.1074\/jbc.M207401200 (2002).","journal-title":"J. Biol. Chem."},{"key":"8796_CR46","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/s41556-020-0488-x","volume":"22","author":"PM M\u00fcller","year":"2020","unstructured":"M\u00fcller, P. M. et al. Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nat. Cell. Biol. 22, 498\u2013511. https:\/\/doi.org\/10.1038\/s41556-020-0488-x (2020).","journal-title":"Nat. Cell. Biol."},{"key":"8796_CR47","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.3892\/ol.2014.2471","volume":"8","author":"W Chen","year":"2014","unstructured":"Chen, W., Mao, K., Liu, Z. & Dinh-Xuan, A. T. The role of the rhoa\/rho kinase pathway in angiogenesis and its potential value in prostate cancer (Review). Oncol. Lett. 8, 1907\u20131911. https:\/\/doi.org\/10.3892\/ol.2014.2471 (2014).","journal-title":"Oncol. Lett."},{"key":"8796_CR48","doi-asserted-by":"publisher","first-page":"3186","DOI":"10.1096\/fj.09-145102","volume":"24","author":"BA Bryan","year":"2010","unstructured":"Bryan, B. A. et al. RhoA\/ROCK signaling is essential for multiple aspects of VEGF-mediated angiogenesis. FASEB Journal: Official Publication Federation Am. Soc. Experimental Biology. 24, 3186\u20133195. https:\/\/doi.org\/10.1096\/fj.09-145102 (2010).","journal-title":"FASEB Journal: Official Publication Federation Am. Soc. Experimental Biology"},{"key":"8796_CR49","doi-asserted-by":"publisher","first-page":"4612","DOI":"10.1128\/mcb.02061-05","volume":"26","author":"DR Croft","year":"2006","unstructured":"Croft, D. R. & Olson, M. F. The Rho GTPase effector ROCK regulates Cyclin A, Cyclin D1, and p27Kip1 levels by distinct mechanisms. Mol. Cell. Biol. 26, 4612\u20134627. https:\/\/doi.org\/10.1128\/mcb.02061-05 (2006).","journal-title":"Mol. Cell. Biol."},{"key":"8796_CR50","doi-asserted-by":"publisher","unstructured":"Sun, H., Breslin, J. W., Zhu, J., Yuan, S. Y. & Wu, M. H. Rho and ROCK signaling in VEGF-induced microvascular endothelial hyperpermeability. Microcirculation (New York, N.Y.:) 13, 237\u2013247, ) 13, 237\u2013247, (1994). https:\/\/doi.org\/10.1080\/10739680600556944 (2006).","DOI":"10.1080\/10739680600556944"},{"key":"8796_CR51","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1001\/jamaneurol.2021.1681","volume":"78","author":"AJ Kundishora","year":"2021","unstructured":"Kundishora, A. J. et al. DIAPH1 variants in Non-East Asian patients with sporadic Moyamoya disease. JAMA Neurol. 78, 993\u20131003. https:\/\/doi.org\/10.1001\/jamaneurol.2021.1681 (2021).","journal-title":"JAMA Neurol."},{"key":"8796_CR52","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.ajhg.2014.01.018","volume":"94","author":"D Herv\u00e9","year":"2014","unstructured":"Herv\u00e9, D. et al. Loss of \u03b11\u03b21 soluble guanylate cyclase, the major nitric oxide receptor, leads to Moyamoya and achalasia. Am. J. Hum. Genet. 94, 385\u2013394. https:\/\/doi.org\/10.1016\/j.ajhg.2014.01.018 (2014).","journal-title":"Am. J. Hum. Genet."},{"key":"8796_CR53","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1038\/sj.bjp.0706408","volume":"146","author":"C Guilluy","year":"2005","unstructured":"Guilluy, C. et al. Inhibition of rhoa\/rho kinase pathway is involved in the beneficial effect of sildenafil on pulmonary hypertension. Br. J. Pharmacol. 146, 1010\u20131018. https:\/\/doi.org\/10.1038\/sj.bjp.0706408 (2005).","journal-title":"Br. J. Pharmacol."},{"key":"8796_CR54","doi-asserted-by":"publisher","unstructured":"Mineharu, Y. & Miyamoto, S. RNF213 and GUCY1A3 in Moyamoya disease: key regulators of metabolism, inflammation, and vascular stability. Front. Neurol. 12\u20132021. https:\/\/doi.org\/10.3389\/fneur.2021.687088 (2021).","DOI":"10.3389\/fneur.2021.687088"},{"key":"8796_CR55","doi-asserted-by":"publisher","first-page":"4674","DOI":"10.1093\/brain\/awad225","volume":"146","author":"F Ye","year":"2023","unstructured":"Ye, F. et al. RNF213 loss-of-function promotes pathological angiogenesis in Moyamoya disease via the Hippo pathway. Brain 146, 4674\u20134689. https:\/\/doi.org\/10.1093\/brain\/awad225 (2023).","journal-title":"Brain"},{"key":"8796_CR56","doi-asserted-by":"publisher","first-page":"e0163561","DOI":"10.1371\/journal.pone.0163561","volume":"11","author":"S Hamauchi","year":"2016","unstructured":"Hamauchi, S. et al. Cellular functions and gene and protein expression profiles in endothelial cells derived from Moyamoya Disease-Specific iPS cells. PLOS ONE. 11, e0163561. https:\/\/doi.org\/10.1371\/journal.pone.0163561 (2016).","journal-title":"PLOS ONE"},{"key":"8796_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2045-824x-4-1","volume":"4","author":"GA Howe","year":"2012","unstructured":"Howe, G. A. & Addison, C. L. RhoB controls endothelial cell morphogenesis in part via negative regulation of RhoA. Vascular Cell. 4, 1. https:\/\/doi.org\/10.1186\/2045-824x-4-1 (2012).","journal-title":"Vascular Cell."},{"key":"8796_CR58","doi-asserted-by":"publisher","first-page":"e102382","DOI":"10.1371\/journal.pone.0102382","volume":"9","author":"D Dai","year":"2014","unstructured":"Dai, D. et al. Serum MiRNA signature in Moyamoya disease. PLoS One. 9, e102382. https:\/\/doi.org\/10.1371\/journal.pone.0102382 (2014).","journal-title":"PLoS One"},{"key":"8796_CR59","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1016\/j.jstrokecerebrovasdis.2015.01.041","volume":"24","author":"S Zhao","year":"2015","unstructured":"Zhao, S. et al. Elevated serum MicroRNA Let-7c in Moyamoya disease. J. Stroke Cerebrovasc. Dis. 24, 1709\u20131714. https:\/\/doi.org\/10.1016\/j.jstrokecerebrovasdis.2015.01.041 (2015).","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"8796_CR60","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12920-018-0385-3","volume":"11","author":"H Uchino","year":"2018","unstructured":"Uchino, H. et al. Circulating mirnome profiling in Moyamoya disease-discordant monozygotic twins and endothelial MicroRNA expression analysis using iPS cell line. BMC Med. Genomics. 11, 72. https:\/\/doi.org\/10.1186\/s12920-018-0385-3 (2018).","journal-title":"BMC Med. Genomics"},{"key":"8796_CR61","doi-asserted-by":"publisher","unstructured":"Melero-Martin, J. M. Human endothelial Colony-Forming cells. Cold Spring Harb Perspect. Med. 12 https:\/\/doi.org\/10.1101\/cshperspect.a041154 (2022).","DOI":"10.1101\/cshperspect.a041154"},{"key":"8796_CR62","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1186\/s12967-024-05108-8","volume":"22","author":"Y Liu","year":"2024","unstructured":"Liu, Y., Lyons, C. J., Ayu, C. & O\u2019Brien, T. Recent advances in endothelial colony-forming cells: from the transcriptomic perspective. J. Transl Med. 22, 313. https:\/\/doi.org\/10.1186\/s12967-024-05108-8 (2024).","journal-title":"J. Transl Med."},{"key":"8796_CR63","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/jnr.22228","volume":"88","author":"JH Kim","year":"2010","unstructured":"Kim, J. H. et al. Decreased level and defective function of Circulating endothelial progenitor cells in children with Moyamoya disease. J. Neurosci. Res. 88, 510\u2013518. https:\/\/doi.org\/10.1002\/jnr.22228 (2010).","journal-title":"J. Neurosci. Res."},{"key":"8796_CR64","doi-asserted-by":"publisher","first-page":"204","DOI":"10.3171\/2018.8.Peds1883","volume":"23","author":"SA Choi","year":"2018","unstructured":"Choi, S. A. et al. Impaired functional recovery of endothelial colony-forming cells from Moyamoya disease in a chronic cerebral hypoperfusion rat model. J. Neurosurg. Pediatr. 23, 204\u2013213. https:\/\/doi.org\/10.3171\/2018.8.Peds1883 (2018).","journal-title":"J. Neurosurg. Pediatr."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-08796-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-08796-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-08796-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:22:04Z","timestamp":1752139324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-08796-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8796"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-08796-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]},"assertion":[{"value":"2 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All protocols involving human specimens were conducted in accordance with the principles outlined in the Declaration of Helsinki. This study received ethical approval from the Institutional Review Board (IRB) of Seoul National University Hospital (IRB No. 1904-096-1027). Informed consent was obtained from all participants involved in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"24655"}}