{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:19:58Z","timestamp":1792113598543,"version":"4.4.0"},"reference-count":0,"publisher":"IMR Press","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HSF"],"abstract":"<jats:p>&lt;p&gt;&lt;strong&gt;Background:\u00a0 &lt;\/strong&gt;Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized.\u00a0 We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients.&lt;\/p&gt;&lt;p&gt;&lt;strong&gt;Methods:\u00a0 &lt;\/strong&gt;Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves. \u00a0Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays.\u00a0 Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test. \u00a0&lt;\/p&gt;&lt;p&gt;&lt;strong&gt;Results:\u00a0 &lt;\/strong&gt;Twenty-seven probes in 9 genes showed significant differential methylation and expression (P&amp;lt;5.5x10&lt;sup&gt;-4&lt;\/sup&gt;).\u00a0 The top gene was protein tyrosine phosphatase, non-receptor type 22 (&lt;em&gt;PTPN22&lt;\/em&gt;), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10&lt;sup&gt;-5&lt;\/sup&gt;) in bicuspid patients, as compared to tricuspid patients.\u00a0 Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including &lt;em&gt;ACTA2&lt;\/em&gt; (4 probes, delta beta range:\u00a0 -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissections&lt;\/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:\u00a0 &lt;\/strong&gt;Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms.\u00a0 The top gene was &lt;em&gt;PTPN22&lt;\/em&gt;, which is involved in T-cell receptor signaling and associated with various immune disorders.\u00a0 These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.&lt;\/p&gt;<\/jats:p>","DOI":"10.1532\/hsf.1247","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T08:23:11Z","timestamp":1441182191000},"page":"134","source":"Crossref","is-referenced-by-count":25,"title":["Epigenetic Profiling Identifies Novel Genes for Ascending Aortic Aneurysm Formation with Bicuspid Aortic Valves"],"prefix":"10.31083","volume":"18","author":[{"given":"Asad A","family":"Shah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2015,9,1]]},"container-title":["The Heart Surgery Forum"],"original-title":[],"link":[{"URL":"http:\/\/journal.hsforum.com\/index.php\/HSF\/article\/viewFile\/1247\/E134-E139","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T10:13:38Z","timestamp":1766398418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/HSF\/18\/4\/10.1532\/hsf.1247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,1]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,9,1]]}},"URL":"https:\/\/doi.org\/10.1532\/hsf.1247","relation":{},"ISSN":["1522-6662","1098-3511"],"issn-type":[{"value":"1522-6662","type":"electronic"},{"value":"1098-3511","type":"print"}],"subject":[],"published":{"date-parts":[[2015,9,1]]}}}