title: Bicuspid Aortic Valve Morphotype Correlates With Regional Antioxidant Gene Expression Profiles in the Proximal Ascending Aorta.
abstract: BACKGROUND
  Bicuspid aortic valve (BAV) is associated with asymmetric dilatation of the proximal ascending aorta. We previously demonstrated increased susceptibility of smooth muscle cells to oxidative stress in the BAV-aneurysmal aorta and hypothesized that antioxidant expression is regionally defined and influenced by the BAV morphotype.
  
  
  METHODS
  BAV valve morphology was defined according to number of raphes: type 0 (0 raphes), type 1 (1 raphe), or type 2 (2 raphes) and by the raphe location among the left (L), right (R) or non (N) coronary cusps. Ascending aortic specimens were partitioned into three regions corresponding to the sinuses of Valsalva, denoted R, N (greater curve), and L (lesser curve). Transcripts 1, 2, and 3 from the gene expressing superoxide dismutase (Sod) were quantified in all three regions. Results were compared with aneurysmal and nonaneurysmal aortic specimens from patients with a tricuspid aortic valve.
  
  
  RESULTS
  Region-specific Sod1 upregulation and Sod2 downregulation were dependent on the BAV morphotype. Sod3 was uniformly downregulated in all regions in a morphotype-independent manner. Sod1 upregulation was noted in the R region of the nonaneurysmal type 1 L/R morphotype. Aortic valve regurgitation, but not stenosis, affected the expression of Sod isoforms in specimens of degenerative aneurysms.
  
  
  CONCLUSIONS
  Region-specific transcription profiles of Sod on the basis of BAV morphotype deepen our understanding of its associated aortopathy and provide biological insight on the asymmetric dilatation pattern. This work indicates regional differences exist in the oxidative stress biology of the proximal aortic wall, and this may lead to newer diagnostic techniques to adjudicate aortic catastrophe risk.
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, McGowan Institute for Regenerative Medicine, and Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Phillippi
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Hill
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Marie
authors.initials: M
authors.lastname: Billaud
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Green
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Kotlarczyk
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, McGowan Institute for Regenerative Medicine, and Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: gleasontg@upmc.edu.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gleason
mesh_terms: D000368:Aged; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging / Q000378:metabolism*; D017545:Aortic Aneurysm, Thoracic / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D001021:Aortic Valve / Q000002:abnormalities*; D000082882:Bicuspid Aortic Valve Disease; D000072226:Computed Tomography Angiography; D004452:Echocardiography; D005260:Female; D005786:Gene Expression Regulation; D006349:Heart Valve Diseases / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D000072105:Superoxide Dismutase-1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C000606290:SOD1 protein, human; D012313:RNA; D000072105:Superoxide Dismutase-1