title: Extracellular matrix fiber microarchitecture is region-specific in bicuspid aortic valve-associated ascending aortopathy.
abstract: OBJECTIVE
  Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) commonly dilate asymmetrically compared with patients with tricuspid aortic valve (TAV). This discrepancy in aneurysm geometry led us to hypothesize that microarchitectural differences underlie the observed asymmetric dilatation pattern. The purpose of this study was to characterize the microarchitectural distinctions of the extracellular matrix of the 2 phenotypes with a focus on the proportion of radially oriented elastin and collagen fibers in different circumferential aortic regions.
  
  
  METHODS
  Aortic tissue rings were obtained just distal to the sinotubular junction from patients with BAV or TAV undergoing elective aneurysm repair. They were sectioned into three circumferentially based regions according to adjacent aortic sinus segment (left coronary sinus [L], right coronary sinus [R], or noncoronary sinus [N]). Multiphoton microscopy was used to quantify and characterize the number of radially oriented elastin and collagen fibers.
  
  
  RESULTS
  There were fewer radially oriented fibers in medial region N and medial-intimal region R of BAV-ATAAs when compared with TAV-ATAAs (medial region N, amplitude of angular undulation of elastin = 10.67° ± 1.35° vs 15.58° ± 1.91°; P = .041; medial-intimal region R, amplitude of angular undulation of elastin = 9.83° ± 0.83° vs 14.72° ± 1.64°; P = .015). Conversely, fibers became more radially oriented in the medial-intimal region L of BAV-ATAA when compared with TAV-ATAA (amplitude of angular undulation of collagen = 18.67° ± 0.95° vs 14.56° ± 1.37°; P = .041).
  
  
  CONCLUSIONS
  The differential pattern of fiber orientation noted between L and N-R regions help explain the unique pattern of greater curvature dilatation of BAV-ATAA. The distinctions noted in matrix microarchitecture may form the basis of differing aneurysm geometries and aortic wall integrities in ATAAs arising in these different valve morphologies.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Alkiviadis
authors.initials: A
authors.lastname: Tsamis
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Phillippi
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Koch
authors.affiliation: Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Chan
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Krawiec
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Department of Surgery, University of Pittsburgh, Pittsburgh, Pa; Fondazione Ri.MED, University of Palermo, Palermo, Italy; Department of Chemical, Management, Computer and Mechanical Engineering (DICIGIM), University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Amore
authors.affiliation: Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Department of Surgery, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: William R
authors.initials: WR
authors.lastname: Wagner
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa; Department of Surgery, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: David A
authors.initials: DA
authors.lastname: Vorp
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pa; Center for Vascular Remodeling and Regeneration, University of Pittsburgh, Pittsburgh, Pa; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pa; Department of Cardiothoracic Surgery, 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; D000369:Aged, 80 and over; D001013:Aorta, Thoracic / Q000473:pathology* / Q000503:physiopathology; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D001021:Aortic Valve / Q000002:abnormalities*; D000082882:Bicuspid Aortic Valve Disease; D004548:Elasticity; D005109:Extracellular Matrix / Q000648:ultrastructure*; D005260:Female; D006349:Heart Valve Diseases / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged
keywords: aortic wall microarchitecture; aortopathy; ascending aortic aneurysm; bicuspid aortic valve; collagen; elastin