{"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":1776539558520,"version":"3.51.2"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,6,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The blood flow rate of brain arteriovenous malformations (\n              <jats:styled-content style=\"fixed-case\">bAVM<\/jats:styled-content>\n              s) is an important clinical characteristic closely associated with the hemorrhage risk and radiosurgery obliteration rate of\n              <jats:styled-content style=\"fixed-case\">bAVM<\/jats:styled-content>\n              s. However, the underlying molecular properties remain unclear. To identify potential key molecules, signaling pathways, and vascular cell types involved, we compared gene expression profiles between\n              <jats:styled-content style=\"fixed-case\">bAVM<\/jats:styled-content>\n              s with high flow rates and low flow rates (\n              <jats:styled-content style=\"fixed-case\">LFR<\/jats:styled-content>\n              ) and validated the functions of selected key molecules in\u00a0vitro.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We performed\n              <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n              \u2010sequencing analysis on 51 samples, including 14 high flow rate\n              <jats:styled-content style=\"fixed-case\">bAVM<\/jats:styled-content>\n              s and 37\n              <jats:styled-content style=\"fixed-case\">LFR bAVM<\/jats:styled-content>\n              s. Functional pathway analysis was performed to identify potential signals influencing the flow rate phenotype of\n              <jats:styled-content style=\"fixed-case\">bAVM<\/jats:styled-content>\n              s. Candidate genes were investigated in\n              <jats:styled-content style=\"fixed-case\">bAVM<\/jats:styled-content>\n              specimens by immunohistochemical staining. Migration, tube formation, and proliferation assays were used to test the effects of candidate genes on the phenotypic properties of cultured human umbilical vein endothelial cells and human brain vascular smooth muscle cells. We identified 250 upregulated and 118 downregulated genes in\n              <jats:styled-content style=\"fixed-case\">LFR bAVM<\/jats:styled-content>\n              s compared with high flow rate\n              <jats:styled-content style=\"fixed-case\">bAVM<\/jats:styled-content>\n              s. Wnt signaling was activated in the\n              <jats:styled-content style=\"fixed-case\">LFR<\/jats:styled-content>\n              group via upregulation of\n              <jats:styled-content style=\"fixed-case\">FZD<\/jats:styled-content>\n              10 and\n              <jats:styled-content style=\"fixed-case\">MYOC<\/jats:styled-content>\n              . Immunohistochemical staining showed that vascular endothelial and smooth muscle cells of\n              <jats:styled-content style=\"fixed-case\">LFR bAVM<\/jats:styled-content>\n              s exhibited increased\n              <jats:styled-content style=\"fixed-case\">FZD<\/jats:styled-content>\n              10 and\n              <jats:styled-content style=\"fixed-case\">MYOC<\/jats:styled-content>\n              expression. Experimentally elevating these genes promoted human umbilical vein endothelial cells and migration and tube formation by activating canonical Wnt signaling in\u00a0vitro.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Our results suggest that canonical Wnt signaling mediated by\n              <jats:styled-content style=\"fixed-case\">FZD<\/jats:styled-content>\n              10 and\n              <jats:styled-content style=\"fixed-case\">MYOC<\/jats:styled-content>\n              is activated in vascular endothelial and smooth muscle cells in\n              <jats:styled-content style=\"fixed-case\">LFR bAVM<\/jats:styled-content>\n              s.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.012746","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T09:00:17Z","timestamp":1559898017000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations"],"prefix":"10.1161","volume":"8","author":[{"given":"Ran","family":"Huo","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases Beijing China"},{"name":"Center of Stroke Beijing Institute for Brain Disorders Beijing China"},{"name":"Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease Beijing 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