{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T19:12:38Z","timestamp":1776539558461,"version":"3.51.2"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Interventional treatment of unruptured brain arteriovenous malformations (BAVMs) has become increasingly controversial. Because medical therapy is still lacking, we aimed to obtain insight into the disease mechanisms implicated in BAVMs and to identify potential targets for medical treatment to prevent rupture of a BAVM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              We used next-generation RNA sequencing to identify differential expression on a transcriptome-wide level comparing tissue samples of 12 BAVMs to 16 intracranial control arteries. We identified differentially expressed genes by negative binominal generalized log-linear regression (false discovery rate corrected\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). We selected 10 genes for validation using droplet digital polymerase chain reaction. We performed functional pathway analysis accounting for potential gene-length bias, to establish enhancement of biological pathways involved in BAVMs. We further assessed which Gene Ontology terms were enriched.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              We found 736 upregulated genes in BAVMs including genes implicated in the cytoskeletal machinery and cell-migration and genes encoding for inflammatory cytokines and secretory products of neutrophils and macrophages. Furthermore, we found 498 genes downregulated including genes implicated in extracellular matrix composition, the binary angiopoietin-TIE system, and TGF (transforming growth factor)-\u03b2 signaling. We confirmed the differential expression of top 10 ranked genes. Functional pathway analysis showed enrichment of the protein digestion and absorption pathway (false discovery rate-adjusted\n              <jats:italic>P<\/jats:italic>\n              =1.70\u00d710\n              <jats:sup>\u22122<\/jats:sup>\n              ). We identified 47 enriched Gene Ontology terms (false discovery rate-adjusted\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05) implicated in cytoskeleton network, cell-migration, endoplasmic reticulum, transmembrane transport, and extracellular matrix composition.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our genome-wide RNA-sequencing study points to involvement of inflammatory mediators, loss of cerebrovascular quiescence, and impaired integrity of the vascular wall in the pathophysiology of BAVMs. Our study may lend support to potential receptivity of BAVMs to medical therapeutics, including those promoting vessel maturation, and anti-inflammatory and immune-modifying drugs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.119.025657","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T10:00:25Z","timestamp":1575453625000},"page":"268-274","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["RNA-Sequencing Highlights Inflammation and Impaired Integrity of the Vascular Wall in Brain Arteriovenous Malformations"],"prefix":"10.1161","volume":"51","author":[{"given":"Allard J.","family":"Hauer","sequence":"first","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Kleinloog","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Giuliani","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabri\u00ebl J.E.","family":"Rinkel","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard A.","family":"de Kort","sequence":"additional","affiliation":[{"name":"Brain Center Rudolf Magnus and Department of Radiology (G.A.d.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan Willem","family":"Berkelbach van der Sprenkel","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"van der Zwan","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"Gosselaar","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C.","family":"van Rijen","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelkje J.","family":"de Boer-Bergsma","sequence":"additional","affiliation":[{"name":"Department of Genetics (J.J.d.B.-B., P.D., M.A.S.), University Medical Center Groningen, the Netherlands"},{"name":"Genomics Coordination Center (J.J.d.B.-B., P.D., M.A.S.), University Medical Center Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Deelen","sequence":"additional","affiliation":[{"name":"Department of Genetics (J.J.d.B.-B., P.D., M.A.S.), University Medical Center Groningen, the Netherlands"},{"name":"Genomics Coordination Center (J.J.d.B.-B., P.D., M.A.S.), University Medical Center Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morris A.","family":"Swertz","sequence":"additional","affiliation":[{"name":"Department of Genetics (J.J.d.B.-B., P.D., M.A.S.), University Medical Center Groningen, the Netherlands"},{"name":"Genomics Coordination Center (J.J.d.B.-B., P.D., M.A.S.), University Medical Center Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"De Muynck","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Leuven and Laboratory of Neurobiology, Center for Brain &amp; Disease Research, VIB and KU Leuven, Belgium (L.D.M., P.V.D.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Van Damme","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Leuven and Laboratory of Neurobiology, Center for Brain &amp; Disease Research, VIB and KU Leuven, Belgium (L.D.M., P.V.D.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan H.","family":"Veldink","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ynte M.","family":"Ruigrok","sequence":"additional","affiliation":[{"name":"From the Department of Neurology and Neurosurgery (A.J.H., R.K., F.G., G.J.E.R., J.W.B.v.d.S., A.v.d.Z., P.H.G., P.C.v.R., J.H.V., Y.M.R., C.J.M.K.), University Medical Center Utrecht, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina J.M.","family":"Klijn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute of Brain Cognition &amp; Behaviour, Center for Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands 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