{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:39:49Z","timestamp":1792690789284,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T00:00:00Z","timestamp":1416268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2014,12]]},"abstract":"Abstract<\/jats:title>Objective<\/jats:title>Brain arteriovenous malformations (AVM<\/jats:styled-content>s) are devastating, hemorrhage\u2010prone, cerebrovascular lesions characterized by well\u2010defined feeding arteries, draining vein(s) and the absence of a capillary bed. The endothelial cells (EC<\/jats:styled-content>s) that comprise AVM<\/jats:styled-content>s exhibit a loss of arterial and venous specification. Given the role of the transcription factor COUP<\/jats:styled-content>\u2010TFII<\/jats:styled-content> in vascular development, EC<\/jats:styled-content> specification, and pathological angiogenesis, we examined human AVM<\/jats:styled-content> tissue to determine if COUP<\/jats:styled-content>\u2010FTII<\/jats:styled-content> may have a role in AVM<\/jats:styled-content> disease biology.<\/jats:p><\/jats:sec>Methods<\/jats:title>We examined 40 human brain AVMs by immunohistochemistry (IHC) and qRT<\/jats:styled-content>\u2010PCR for the expression of COUP\u2010TFII as well as other genes involved in venous and lymphatic development, maintenance, and signaling. We also examined proliferation and EC tube formation with human umbilical ECs (HUVEC) following COUP\u2010TFII overexpression.<\/jats:p><\/jats:sec>Results<\/jats:title>We report that AVM<\/jats:styled-content>s expressed COUP<\/jats:styled-content>\u2010TFII<\/jats:styled-content>, SOX<\/jats:styled-content>18, PROX<\/jats:styled-content>1, NFATC<\/jats:styled-content>1, FOXC<\/jats:styled-content>2, TBX<\/jats:styled-content>1, LYVE<\/jats:styled-content>1, Podoplanin, and vascular endothelial growth factor (VEGF<\/jats:styled-content>)\u2010C, contained Ki67\u2010positive cells and heterogeneously expressed genes involved in Hedgehog, Notch, Wnt, and VEGF<\/jats:styled-content> signaling pathways. Overexpression of COUP<\/jats:styled-content>\u2010TFII<\/jats:styled-content> alone in vitro resulted in increased EC<\/jats:styled-content> proliferation and dilated tubes in an EC<\/jats:styled-content> tube formation assay in HUVEC<\/jats:styled-content>.<\/jats:p><\/jats:sec>Interpretation<\/jats:title>This suggests AVM EC<\/jats:styled-content>s are further losing their arterial\/venous specificity and acquiring a partial lymphatic molecular phenotype. There was significant correlation of gene expression with presence of clinical edema and acute hemorrhage. While the precise role of these genes in the formation, stabilization, growth and risk of hemorrhage of AVM<\/jats:styled-content>s remains unclear, these findings have potentially important implications for patient management and treatment choice, and opens new avenues for future work on AVM<\/jats:styled-content> disease mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.142","type":"journal-article","created":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T08:49:28Z","timestamp":1416300568000},"page":"982-995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Human brain arteriovenous malformations express lymphatic\u2010associated genes"],"prefix":"10.1002","volume":"1","author":[{"given":"Lorelei D.","family":"Shoemaker","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Stanford Neuromolecular Innovation Program Stanford University 300 Pasteur Drive Stanford California 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