title: Reproducible porcine model of thoracic aortic aneurysm.
abstract: BACKGROUND
  Thoracic aortic aneurysms (TAAs) develop secondary to abnormal aortic extracellular matrix remodeling, resulting in a weakened and dilated aortic wall that progressed to rupture if left unattended. Currently, no diagnostic/prognostic tests are available for the detection of TAA disease. This is largely driven by the lack of a large animal model, which would permit longitudinal/mechanistic studies. Accordingly, the objective of the present study was to establish a reproducible porcine model of aortic dilatation, which recapitulates the structural and biochemical changes observed during human TAA development.
  
  
  RESULTS
  Descending TAAs were induced in Yorkshire pigs (20-25 kg; n=7) through intra-adventitial injections of collagenase (5 mL, 0.35 mg/mL) and periadventitial application of crystalline CaCl2 (0.5 g). Three weeks after TAA induction, aortas were harvested and tissue was collected for biochemical and histological measurements. A subset of animals underwent MRI preoperatively and at terminal surgery. Results were compared with sham-operated controls (n=6). Three weeks after TAA induction, aortic luminal area increased by 38 ± 13% (P=0.018 versus control). Aortic structural changes included elastic lamellar degradation and decreased collagen content. The protein abundance of matrix metalloproteinases 3, 8, 9, and 12 increased in TAA tissue homogenates, whereas tissue inhibitors of metalloproteinases 1 and 4 decreased.
  
  
  CONCLUSIONS
  These data demonstrate aortic dilatation, aortic medial degeneration, and alterations in matrix metalloproteinase/tissue inhibitors of metalloproteinase abundance, consistent with TAA formation. This study establishes for the first time a large animal model of TAA that recapitulates the hallmarks of human disease and provides a reproducible test bed for examining diagnostic, prognostic, and therapeutic strategies.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery (S.R.E., C.B.L., J.M.O., R.K.P., A.D.R., R.E.S., R.M., J.S.I., J.A.J.) and Division of Cardiology, Department of Medicine (W.B.W.), Medical University of South Carolina, Charleston, SC; Research Service, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (J.A.J.); and Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, and Wm. Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC (F.G.S.).
authors.forename: Shaina R
authors.initials: SR
authors.lastname: Eckhouse
authors.forename: Christina B
authors.initials: CB
authors.lastname: Logdon
authors.forename: J Marshall
authors.initials: JM
authors.lastname: Oelsen
authors.forename: Risha K
authors.initials: RK
authors.lastname: Patel
authors.forename: Allison D
authors.initials: AD
authors.lastname: Rice
authors.forename: Robert E
authors.initials: RE
authors.lastname: Stroud
authors.forename: W Benjamin
authors.initials: WB
authors.lastname: Wince
authors.forename: Rupak
authors.initials: R
authors.lastname: Mukherjee
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
authors.forename: John S
authors.initials: JS
authors.lastname: Ikonomidis
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jones
mesh_terms: D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D008297:Male; D015203:Reproducibility of Results; D013552:Swine
keywords: aneurysm; animal models; aortic diseases; cardiovascular disease; remodeling
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