title: Ascending aorta dilation in association with bicuspid aortic valve: a maturation defect of the aortic wall.
abstract: OBJECTIVE
  Patients with a bicuspid aortic valve have increased susceptibility to the development of ascending aortic dilation and dissection compared with persons with a tricuspid valve. To unravel a possible different mechanism underlying dilation in bicuspidy and tricuspidy, a comparison of the structure of the aortic wall was made.
  
  
  METHODS
  Ascending aortic wall biopsies were divided into 4 groups: bicuspid (n=36) and tricuspid (n=23) without and with dilation. The expression of vascular smooth muscle cell maturation markers including lamin A/C, which plays a pivotal role in smooth muscle cell differentiation, and its splicing variant progerin indicative of aging, were studied immunohistochemically. Attention was also paid to the inflammatory status.
  
  
  RESULTS
  There is a significant difference in the structure and maturation of the aortic wall in bicuspidy, persisting in the dilated aortic wall, presenting with a thinner intima, lower expression of α smooth muscle actin, smooth muscle 22α, calponin, and almost absent expression of smoothelin. We show for the first time significantly lowered lamin A/C expression in bicuspidy. Progerin was found to be significantly increased in the media of the dilated wall in tricuspidy, also showing increased periaortic inflammation.
  
  
  CONCLUSIONS
  The structure of the nondilated and dilated aortic wall in bicuspidy and tricuspidy are intrinsically different, with the latter having more aspects of aging. In bicuspidy there is a defective smooth muscle cell differentiation possibly linked to lowered lamin A/C expression. Based on this vessel wall immaturity and increased susceptibility to dilation, different diagnostic and therapeutic approaches are warranted.
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nimrat
authors.initials: N
authors.lastname: Grewal
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Poelmann
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robert J M
authors.initials: RJ
authors.lastname: Klautz
authors.affiliation: Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johannes H N
authors.initials: JH
authors.lastname: Lindeman
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Meindert
authors.initials: M
authors.lastname: Palmen
authors.affiliation: Department of Cardiac and Thoracic Vascular Surgery, University of Lübeck, Lübeck, Germany.
authors.forename: Salah A
authors.initials: SA
authors.lastname: Mohamed
authors.affiliation: Department of Cardiac and Thoracic Vascular Surgery, University of Lübeck, Lübeck, Germany.
authors.forename: Hans-Hinrich
authors.initials: HH
authors.lastname: Sievers
authors.affiliation: Department of Cardiothoracic Surgery and Heart Valve Bank, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Ad J J C
authors.initials: AJ
authors.lastname: Bogers
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.c.deruiter@lumc.nl.
authors.forename: Marco C
authors.initials: MC
authors.lastname: DeRuiter
mesh_terms: D000368:Aged; D001013:Aorta, Thoracic / Q000473:pathology*; D001018:Aortic Diseases / Q000473:pathology*; D001021:Aortic Valve / Q000002:abnormalities* / Q000473:pathology; D000082882:Bicuspid Aortic Valve Disease; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D004108:Dilatation, Pathologic; D005260:Female; D006349:Heart Valve Diseases / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D034904:Lamin Type A / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism
chemical_list: D015415:Biomarkers; C494847:LMNA protein, human; D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A