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The association between Ki\u201067 and <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 expression was also examined. Human umbilical vein endothelial cells (<jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s) were treated with a combination of lipopolysaccharide and resveratrol (a <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 activator) or sirtinol (a <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 inhibitor); and the levels of <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>s encoding <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin were determined. <jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content> tube formation was assayed in the presence of resveratrol or sirtinol. The Mann\u2013Whitney <jats:italic>U<\/jats:italic>\u2010test or the Tukey\u2013Kramer test was used for statistical analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ki\u201067\u2010expressing cells, including endothelial cells, lay adjacent to <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1\u2010expressing cells in periapical granulomas. In addition, <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1\u2010expressing cells were detected adjacent to <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010expressing cells and <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\u2010 or <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin\u2010expressing endothelial cells. <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression levels in periapical granulomas were significantly higher (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.0054, 0.0090 and 0.0090, respectively) than those in healthy gingival tissues. <jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s treated with resveratrol exhibited significantly higher expression of <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>s encoding <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.0019, 0.00005 and 0.0045, respectively) compared with controls, but sirtinol inhibited such expression. Resveratrol caused <jats:styled-content style=\"fixed-case\">HUVEC<\/jats:styled-content>s to form tube\u2010like structures, whilst sirtinol inhibited this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>1 may stimulate angiogenesis in periapical granulomas by triggering the proliferation of endothelial cells and inducing <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin expression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.12894","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T07:38:43Z","timestamp":1516779523000},"page":"747-757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A potential role for the silent information regulator 2 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