Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells

Q. Yang, M. J. Dahl, K. H. Albertine, R. Ramchandran, M. Sun, J. U. Raj

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13 Scopus citations

Abstract

Objective: Pulmonary arterial hypertension, characterized by pulmonary vascular remodelling and vasoconstriction, is associated with excessive proliferative changes in pulmonary vascular walls. However, the role of HDACs in the phenotypic alteration of pulmonary arterial smooth muscle cells (PASMC) is largely unknown. Material and methods: Pulmonary arterial smooth muscle cells were isolated from newborn sheep. Cell cycle analysis was performed by flow cytometry. mRNA and protein expression were measured by real-time PCR and Western blot analysis. Wound-healing scratch assay was used to measure cell migration. Contractility of newborn PASMCs was determined by gel contraction assay. Chromatin immunoprecipitation was used to examine histone modifications along the p21 promoter region. Global DNA methylation was measured by liquid chromatography-mass spectroscopy. Results: Inhibition of class I and class II HDACs by apicidin and HDACi VIII suppressed proliferation of newborn PASMC and induced cell cycle arrest in G1 phase. Acetyl H3 levels were higher in newborn PASMC treated with apicidin and HDACi VIII. This was accompanied by increased expression of p21 and reduced expression of CCND1 but not p53. HDAC inhibition altered histone codes around the p21 promoter region in NPASMC. Apicidin inhibited serum-induced cell migration, and modulated profiling of expression of genes encoding pro-oxidant and antioxidant enzymes. Contractility and global DNA methylation levels of newborn PASMCs were also markedly modulated by apicidin. Conclusion: Our results demonstrate that class I HDACs are clearly involved in phenotypic alteration of newborn PASMC.

Original languageEnglish (US)
Pages (from-to)654-664
Number of pages11
JournalCell Proliferation
Volume46
Issue number6
DOIs
StatePublished - Dec 1 2013

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Yang, Q., Dahl, M. J., Albertine, K. H., Ramchandran, R., Sun, M., & Raj, J. U. (2013). Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells. Cell Proliferation, 46(6), 654-664. https://doi.org/10.1111/cpr.12076