{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:38:21Z","timestamp":1791214701821,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Pulmonary arterial hypertension, characterized by pulmonary vascular remodelling and vasoconstriction, is associated with excessive proliferative changes in pulmonary vascular walls. However, the role of <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s in the phenotypic alteration of pulmonary arterial smooth muscle cells (<jats:styled-content style=\"fixed-case\">PASMC<\/jats:styled-content>) is largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>Pulmonary arterial smooth muscle cells were isolated from newborn sheep. Cell cycle analysis was performed by flow cytometry. <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein expression were measured by real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and Western blot analysis. Wound\u2010healing scratch assay was used to measure cell migration. Contractility of newborn <jats:styled-content style=\"fixed-case\">PASMC<\/jats:styled-content>s was determined by gel contraction assay. Chromatin immunoprecipitation was used to examine histone modifications along the <jats:italic>p21<\/jats:italic> promoter region. Global <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation was measured by liquid chromatography\u2010mass spectroscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inhibition of class I and class II <jats:styled-content style=\"fixed-case\">HDACs<\/jats:styled-content> by apicidin and <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>i VIII suppressed proliferation of newborn <jats:styled-content style=\"fixed-case\">PASMC<\/jats:styled-content> and induced cell cycle arrest in G<jats:sub>1<\/jats:sub> phase. Acetyl H3 levels were higher in newborn <jats:styled-content style=\"fixed-case\">PASMC<\/jats:styled-content> treated with apicidin and <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>i VIII. This was accompanied by increased expression of <jats:italic>p21<\/jats:italic> and reduced expression of <jats:italic>CCND1<\/jats:italic> but not <jats:italic>p53<\/jats:italic>. <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content> inhibition altered histone codes around the <jats:italic>p21<\/jats:italic> promoter region in <jats:styled-content style=\"fixed-case\">NPASMC<\/jats:styled-content>. Apicidin inhibited serum\u2010induced cell migration, and modulated profiling of expression of genes encoding pro\u2010oxidant and antioxidant enzymes. Contractility and global <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation levels of newborn <jats:styled-content style=\"fixed-case\">PASMC<\/jats:styled-content>s were also markedly modulated by apicidin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that class I <jats:styled-content style=\"fixed-case\">HDACs<\/jats:styled-content> are clearly involved in phenotypic alteration of newborn <jats:styled-content style=\"fixed-case\">PASMC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12076","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T16:19:57Z","timestamp":1383063597000},"page":"654-664","source":"Crossref","is-referenced-by-count":28,"title":["Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells"],"prefix":"10.1111","volume":"46","author":[{"given":"Q.","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Illinois at Chicago Chicago IL 60612 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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