{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:56:42Z","timestamp":1786636602890,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mitochondrial D\u2010loop methylation leads to abnormal cerebral angiogenesis. This study examines its role in vascular phenotypes of moyamoya disease (MMD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Blood samples from 96 intracranial artery stenosis\/occlusion (ICASO) patients (35 MMD, 61 non\u2010MMD) and healthy controls underwent methylation analysis. D\u2010loop methylation levels were analyzed using chi\u2010square,\n                      <jats:italic>T<\/jats:italic>\n                      \u2010test, and Wilcoxon tests. Propensity score matching (PSM) adjusted for age and gender disparities. Combine clinical information with methylation data to build a diagnostic model. Further studies included the methylation levels in MMD patients carrying the RNF213 p.R4810K mutation and the methylation levels and possible mechanisms of human brain microvascular endothelial cells (hCMEC\/D3) with RNF213 knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Healthy controls showed higher D\u2010loop methylation than MMD (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). Post\u2010PSM, non\u2010MMD ICASO patients showed higher D\u2010loop methylation than MMD (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). The AUC of the prediction model was 0.891 (95% CI, 0.821\u20130.961) after combining clinical information with methylation data. MMD patients with the RNF213 mutation exhibited reduced methylation at most sites, though not statistically significant (\n                      <jats:italic>p<\/jats:italic>\n                      &gt; 0.05). RNF213 knockout in hCMEC\/D3 enhanced proliferation, migration, and tube formation, while reducing apoptosis and DNMT1 expression, leading to decreased D\u2010loop methylation and ROS level, increased ATP production and mitochondrial membrane potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>There are differences in the methylation levels in the mitochondrial D\u2010loop region between MMD and non\u2010MMD ICASO. The methylation\u2013metabolism\u2013angiogenesis axis may represent a promising research direction for elucidating MMD pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71042","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T07:15:21Z","timestamp":1763795721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on Abnormal Angiogenesis in Moyamoya Disease via Mitochondrial D\u2010Loop Methylation"],"prefix":"10.1002","volume":"15","author":[{"given":"Yuting","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital, Sun Yat\u2010sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases; National Key Clinical Department and Key Discipline of Neurology, No.58 Zhongshan Road 2  Guangzhou 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