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Aneurysm formation in patients with BAV<\/jats:styled-content> and TAV<\/jats:styled-content> is known to be distinct at the molecular level but the underlying mechanisms are undefined. Here, we investigated the still incompletely described role of microRNA<\/jats:styled-content>s (miRNA<\/jats:styled-content>s), important post\u2010transcriptional regulators of gene expression, in such aortic disease of patients with BAV<\/jats:styled-content> as compared with TAV<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods and Results<\/jats:title>Using a system biology approach, based on data obtained from proteomic analysis of non\u2010dilated aortas from BAV<\/jats:styled-content> and TAV<\/jats:styled-content> patients, we constructed a gene\u2010interaction network of regulatory microRNA<\/jats:styled-content>s associated with the observed differential protein signature. The miR\u2010200 family was the highest ranked miRNA<\/jats:styled-content>, hence potentially having the strongest effect on the signalling network associated with BAV<\/jats:styled-content>. Further, qRT<\/jats:styled-content>\u2010PCR<\/jats:styled-content> and ChIP<\/jats:styled-content> analyses showed lower expression of miR\u2010200c, higher expression of miR\u2010200 target genes, ZEB<\/jats:styled-content>1\/ZEB<\/jats:styled-content>2 transcription factors, and higher chromatin occupancy of the miR\u2010200c promoter by ZEB<\/jats:styled-content>1\/ZEB<\/jats:styled-content>2 in BAV<\/jats:styled-content> patients, indicating a miR\u2010200c\/ZEB<\/jats:styled-content>s negative feedback loop and induction of endothelial\/epithelial mesenchymal transition (EndMT<\/jats:styled-content>\/EMT<\/jats:styled-content>).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>We propose that a miR\u2010200\u2010dependent process of EndMT<\/jats:styled-content>\/EMT<\/jats:styled-content> is a plausible biological mechanism rendering the BAV<\/jats:styled-content> ascending aorta more prone to aneurysm development. Although initially supported by a miR\u2010200c\/ZEB<\/jats:styled-content> feedback loop, this process is most probably advanced by cooperation of other miRNA<\/jats:styled-content>s.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12833","type":"journal-article","created":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T02:15:02Z","timestamp":1538532902000},"page":"102-114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The mir\u2010200 family regulates key pathogenic events in ascending aortas of individuals with bicuspid aortic valves"],"prefix":"10.1111","volume":"285","author":[{"given":"S.","family":"Maleki","sequence":"first","affiliation":[{"name":"Department of Medicine Cardiovascular Medicine Unit Center for Molecular Medicine Karolinska Institutet Stockholm Sweden"},{"name":"Karolinska University Hospital Solna Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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