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We have investigated the effect of folate deficiency on VSMCs in two cell culture systems representing early and late stages of smooth muscle cells differentiation. We find that folate deficiency promotes differentiation towards a more contractile phenotype as indicated by increased expression of respective marker genes. However, microarray analysis identified markers of striated muscle as the predominant gene expression change elicited by folate deficiency. These changes are not merely a reflection of cell cycle arrest, as foetal calf serum restriction or iron deficiency do not replicate the gene expression changes observed in response to folate deficiency. Folate deficiency only has a marginal effect on global DNA methylation. DNA methylation of CpG islands associated with genes regulated by folate deficiency remains unaffected. This supports our earlier findings in a mouse model system which also did not show any changes in global DNA methylation in response to folate and vitamin B6\/B12 deficiency. These data suggest that folate deficiency enhances the expression of smooth muscle marker gene expression, promotes a shift towards a skeletal muscle phenotype, and does not regulate gene expression via DNA methylation.<\/jats:p>","DOI":"10.1042\/bcj20190275","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T15:55:12Z","timestamp":1568735712000},"page":"2769-2795","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Folate deficiency promotes differentiation of vascular smooth muscle cells without affecting the methylation status of regulated genes"],"prefix":"10.1042","volume":"476","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9056-5504","authenticated-orcid":false,"given":"Andreas F.","family":"Kolb","sequence":"first","affiliation":[{"name":"Metabolic Health Group, Rowett Institute, University of Aberdeen, Aberdeen AB25 2ZD, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Petrie","sequence":"additional","affiliation":[{"name":"Metabolic Health Group, Rowett Institute, University of Aberdeen, Aberdeen AB25 2ZD, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus D.","family":"Mayer","sequence":"additional","affiliation":[{"name":"Biomathematics and Statistics Scotland (BioSS), University of Aberdeen, Aberdeen AB25 2ZD, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Pirie","sequence":"additional","affiliation":[{"name":"Metabolic Health Group, Rowett Institute, University of Aberdeen, Aberdeen AB25 2ZD, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan J.","family":"Duthie","sequence":"additional","affiliation":[{"name":"Metabolic Health Group, Rowett Institute, University of Aberdeen, Aberdeen AB25 2ZD, U.K."},{"name":"School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen AB10 7GJ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"key":"2021112218004740600_BCJ-2019-0275C1","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.acvd.2009.07.002","article-title":"The controversial role of B-vitamins in cardiovascular risk: an update","volume":"102","year":"2009","journal-title":"Arch. 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