{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:35:00Z","timestamp":1792787700132,"version":"4.5.0"},"reference-count":55,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the National Natural Science Foundation of China","award":["82171196"],"award-info":[{"award-number":["82171196"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Henan Provincial Key Research and Development Special Program","award":["241111313500"],"award-info":[{"award-number":["241111313500"]}]},{"name":"the Henan Provincial Major Project of Medical Science and Technology Key Research Program under Provincial-Ministerial Co-Construction","award":["SBGJ202401002"],"award-info":[{"award-number":["SBGJ202401002"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Previous research has predominantly focused on vascular smooth muscle cell pathology, whereas the role of brain microvascular endothelial cells (BMECs) in the disease remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the impact of the NOTCH3-R544C mutation on BMECs function and to elucidate the underlying mechanisms of endothelial dysfunction in CADASIL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using CADASIL transgenic mice and endothelial cell (EC) models stably expressing NOTCH3-R544C, the impact of the mutation on endothelial function was assessed through immunofluorescence staining, RNA-seq analysis, protein-protein interaction (PPI) network mapping, and lipid and cellular function assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant NOTCH3 extracellular domain (NOTCH3ECD) deposition and reduced microvascular density are observed in CADASIL mice. R544C mutant cells exhibit abnormal NOTCH3ECD accumulation alongside pronounced gene expression dysregulation, predominantly enriched in pathways related to inflammation, cell migration. The PPI network centers on CXCL10 as a pivotal hub, forming a core \u201cinflammation-migration\u201d pathological axis. R544C cells exhibit heightened inflammatory responses, cholesterol accumulation, reduced cell viability, and increased sensitivity to inflammatory stimuli.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The NOTCH3-R544C mutation disrupts inflammatory regulation, migratory capacity, and lipid metabolic homeostasis in BMECs, leading to endothelial dysfunction and revealing a key mechanism of endothelial injury in CADASIL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261444309","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:01:16Z","timestamp":1776780076000},"page":"1792-1806","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["NOTCH3-R544C mutation drives endothelial dysfunction through inflammation, migration impairment, and lipid dysregulation"],"prefix":"10.1177","volume":"111","author":[{"given":"Ruihua","family":"Sun","sequence":"first","affiliation":[{"name":"Henan Provincial People's Hospital & Zhengzhou University People's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyue","family":"Li","sequence":"additional","affiliation":[{"name":"Henan Provincial People's Hospital & People's Hospital of Zhengzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nanyang Central Hospital, Nanyang, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Ji","sequence":"additional","affiliation":[{"name":"Henan Provincial People's Hospital & Zhengzhou University People's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenxiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Henan Provincial 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