title: Mechanism of aortic medial matrix remodeling is distinct in patients with bicuspid aortic valve.
abstract: OBJECTIVE
  Patients with bicuspid aortic valves (BAV) are predisposed to developing ascending thoracic aortic aneurysms (TAA) at an earlier age than patients who develop degenerative TAAs and have a tricuspid aortic valve (TAV). The hypothesis tested is that BAV-associated aortopathy is mediated by a mechanism of matrix remodeling that is distinct from that seen in TAAs of patients with tricuspid aortic valves.
  
  
  METHODS
  Aortic specimens were collected during ascending aortic replacement, aortic valve replacement, and heart transplants from nonaneurysmal (NA) donors and recipients. Matrix architecture of the aortic media was assessed qualitatively using multiphoton microscopy followed by quantification of collagen and elastin fiber orientation. α-Elastin was determined and matrix maturity was assessed by quantifying immature and mature collagen and lysyl oxidase (Lox) expression and activity in aortic specimens. Matrix metalloproteinase-2/9 activity was quantified in aortic smooth muscle cells.
  
  
  RESULTS
  Elastin and collagen fibers were more highly aligned in BAV-NA and BAV-TAA cases than in TAV-TAA cases, whereas TAV-TAA cases were more disorganized than TAV-NA cases. α-Elastin content was unchanged. Immature collagen was reduced in BAV-NA and BAV-TAA cases when compared with TAV-NA and TAV-TAA cases. Mature collagen was elevated in TAV-TAA cases compared with TAV-NA and BAV-TAA cases. There was a trend toward elevated Lox gene expression and activity and matrix metalloproteinase-2/9 activity for TAV-TAA, BAV-NA, and BAV-TAA specimens.
  
  
  CONCLUSIONS
  The highly aligned matrix architecture in patients with BAVs indicates that wall remodeling is distinct from TAV-TAA. Altered matrix architecture and reduced collagen maturity suggest that the effector molecules mediating the remodeling of TAAs are different in BAV and TAV cases.
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Thoracic Aortic Disease, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Phillippi
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Green
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Eskay
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Kotlarczyk
authors.affiliation: Institute for Computational Engineering and Sciences, University of Texas, Austin, Tex.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hill
authors.affiliation: Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Robertson
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: David A
authors.initials: DA
authors.lastname: Vorp
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Thoracic Aortic Disease, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa. Electronic address: gleasontg@upmc.edu.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Gleason
mesh_terms: D000328:Adult; D000368:Aged; D001013:Aorta, Thoracic / Q000737:chemistry / Q000473:pathology*; D001018:Aortic Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001021:Aortic Valve / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D000082882:Bicuspid Aortic Valve Disease; D015415:Biomarkers / Q000032:analysis; D003094:Collagen / Q000032:analysis; D004549:Elastin / Q000032:analysis; D005260:Female; D006349:Heart Valve Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D008249:Protein-Lysine 6-Oxidase / Q000032:analysis / Q000235:genetics; D017540:Tunica Media / Q000737:chemistry / Q000473:pathology*
chemical_list: D015415:Biomarkers; D003094:Collagen; D004549:Elastin; D008249:Protein-Lysine 6-Oxidase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9