title: Histone acetylation and histone acetyltransferases show significant alterations in human abdominal aortic aneurysm.
abstract: BACKGROUND
  Epigenetic modifications may play a relevant role in the pathogenesis of human abdominal aortic aneurysm (AAA). The aim of the study was therefore to investigate histone acetylation and expression of corresponding lysine [K] histone acetyltransferases (KATs) in AAA.
  
  
  RESULTS
  A comparative study of AAA tissue samples (n = 37, open surgical intervention) and healthy aortae (n = 12, trauma surgery) was performed using quantitative PCR, immunohistochemistry (IHC), and Western blot. Expression of the KAT families GNAT (KAT2A, KAT2B), p300/CBP (KAT3A, KAT3B), and MYST (KAT5, KAT6A, KAT6B, KAT7, KAT8) was significantly higher in AAA than in controls (P ≤ 0.019). Highest expression was observed for KAT2B, KAT3A, KAT3B, and KAT6B (P ≤ 0.007). Expression of KAT2B significantly correlated with KAT3A, KAT3B, and KAT6B (r = 0.705, 0.564, and 0.528, respectively, P < 0.001), and KAT6B with KAT3A, KAT3B, and KAT6A (r = 0.407, 0.500, and 0.531, respectively, P < 0.05). Localization of highly expressed KAT2B, KAT3B, and KAT6B was further characterized by immunostaining. Significant correlations were observed between KAT2B with endothelial cells (ECs) (r = 0.486, P < 0.01), KAT3B with T cells and macrophages, (r = 0.421 and r = 0.351, respectively, P < 0.05), KAT6A with intramural ECs (r = 0.541, P < 0.001) and with a contractile phenotype of smooth muscle cells (SMCs) (r = 0.425, P < 0.01), and KAT6B with T cells (r = 0.553, P < 0.001). Furthermore, KAT2B was associated with AAA diameter (r = 0.382, P < 0.05), and KAT3B, KAT6A, and KAT6B correlated negatively with blood urea nitrogen (r = -0.403, -0.408, -0.478, P < 0.05). In addtion, acetylation of the histone substrates H3K9, H3K18 and H3K14 was increased in AAA compared to control aortae.
  
  
  CONCLUSIONS
  Our results demonstrate that aberrant epigenetic modifications such as changes in the expression of KATs and acetylation of corresponding histones are present in AAA. These findings may provide new insight in the pathomechanism of AAA.
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany.|Department of Vascular and Surgery, The First Hospital of China Medical University, Shenyang, China.|Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Yanshuo
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Fadwa
authors.initials: F
authors.lastname: Tanios
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany.|Department for Visceral, Thoracic and Vascular Surgery at the University Hospital, Technical University Dresden, Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Reeps
authors.affiliation: Department of Vascular and Surgery, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Pathology, Klinikum rechts der Isar der Technische Universität München, Munich, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Schwamborn
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Hans-Henning
authors.initials: HH
authors.lastname: Eckstein
authors.affiliation: Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.|Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.affiliation: Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Pelisek
mesh_terms: D000107:Acetylation; D000368:Aged; D001012:Aorta, Abdominal / Q000201:enzymology / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D006657:Histones; D051548:Histone Acetyltransferases
keywords: AAA; Acetyltransferases; Epigenetics; Histone acetylation; KAT/HAT