title: Global histone H3 lysine 27 triple methylation levels are reduced in vessels with advanced atherosclerotic plaques.
abstract: OBJECTIVE
  Alterations in epigenetic processes are frequently noted in human disease. These epigenetic processes involve methylation of DNA and post-translational modifications of histones. It is well established that in particular histone methylation plays a key role in gene transcription. In this study, we have investigated the relationship between triple methylation of lysine 27 in histone H3 (H3K27Me3) modifications and atherosclerotic plaque stage.
  
  
  METHODS
  28 peri-renal aortic tissue patches covering the entire spectrum of atherosclerotic plaque development were evaluated by immunohistochemistry for the levels of H3K27Me3, EZH2, JMJD3 and BMI1.
  
  
  RESULTS
  The results of our studies are in support of a reduction in global levels of the H3K27Me3 modification in vessels with advanced atherosclerotic plaques. This reduction in H3K27Me3 levels is not accompanied by alterations in global levels of the corresponding histone methyltransferase EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2). Likewise no alterations in global levels of BMI1, a component of the PRC1 complex, which binds to H3K27Me3-modified histones or the global expression levels of the histone demethylase JMJD3, which removes the methyl marks on H3K27, were observed.
  
  
  CONCLUSIONS
  Together, our data show that in atherosclerosis development alterations in global levels of H3K27Me3 occur. The reduction in the number of nuclei in the tunica media that display the repressive H3K27Me3 mark in vessels with advanced atherosclerosis plaques therefore could be a reflection of the dynamic pattern of smooth muscle cell differentiation and proliferation associated with atherosclerotic disease.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Wierda
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Inge M
authors.initials: IM
authors.lastname: Rietveld
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marja C J A
authors.initials: MC
authors.lastname: van Eggermond
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeroen A M
authors.initials: JA
authors.lastname: Belien
authors.affiliation: Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Erik W
authors.initials: EW
authors.lastname: van Zwet
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan H N
authors.initials: JH
authors.lastname: Lindeman
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: pjvdelsen@lumc.nl.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
mesh_terms: D000704:Analysis of Variance; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation / Q000502:physiology*; D000071221:Enhancer of Zeste Homolog 2 Protein; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism
chemical_list: D006657:Histones; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7
keywords: Atherosclerosis; Epigenetics; H3K27Me3; Histone H3 lysine 27 trimethylation; Histone methylation; Immunohistochemistry; Polycomb group proteins