{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:24:19Z","timestamp":1766157859420,"version":"3.48.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,12,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Cerebral arteriovenous malformations (cAVMs) are complex vascular anomalies carrying a high risk of hemorrhage due to abnormal arteriovenous connections. Recent studies have highlighted the roles of inflammation and\n                      <jats:italic toggle=\"no\">KRAS<\/jats:italic>\n                      mutations in the pathogenesis of cAVM. Necroptosis is a programmed cell necrosis pathway mediated by RIPK3 (receptor\u2010interacting protein kinase 3) and MLKL (mixed\u2010lineage kinase domain\u2010like protein). The pathway, which is inhibited by caspase\u20108, plays multifunctional roles in various diseases. However, the involvement of necroptosis and its relationship with caspase\u20108 in the pathogenesis of cAVM remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We analyzed tissue samples from 23 patients with cAVM in comparison with normal brain tissues. Proteome profiling, immunohistochemistry, and quantitative polymerase chain reaction assays were used to assess the expression of inflammatory molecules and programmed cell death markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Protein and gene expression of necroptosis\u2010related molecules (RIPK3, MLKL), caspase\u20108, and IL\u20106 (interleukin\u20106) and IL\u20108 were significantly elevated in cAVM nidi compared with normal brain tissue. High MLKL protein expression was associated with severe clinical presentations and hemorrhage, whereas caspase\u20108 protein expression was elevated in less\u2010severe cases and unruptured cAVM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our analysis of human samples offers the first evidence of necroptosis\u2010related molecules acting against caspase\u20108 in association with the inflammatory cytokines IL\u20106 and IL\u20108 in the pathogenesis of cAVM. The balance between MLKL and caspase\u20108 expression may be linked to the clinical condition and hemorrhagic presentation of patients with cAVM on admission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.044575","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T11:02:36Z","timestamp":1765450956000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in Expression Profiles of Caspase\u20108 and Mixed Lineage Kinase Domain\u2010Like Protein\/Receptor\u2010Interacting Protein Kinase 3 Mediated by Inflammation in Cerebral Arteriovenous Malformations Associated With Clinical Condition on Admission"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2262-9243","authenticated-orcid":false,"given":"Kenji","family":"Shimada","sequence":"first","affiliation":[{"name":"Tokushima University","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9005-1570","authenticated-orcid":false,"given":"Izumi","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Tokushima University","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9136-1829","authenticated-orcid":false,"given":"Takeshi","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Tokushima University","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5326-3467","authenticated-orcid":false,"given":"Masaaki","family":"Korai","sequence":"additional","affiliation":[{"name":"Tokushima University","place":["Tokushima, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Koyama","sequence":"additional","affiliation":[{"name":"Tokushima University","place":["Tokushima, 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