title: A novel chronic advanced stage abdominal aortic aneurysm murine model.
abstract: The purpose of this study was to establish a reliable, chronic model of abdominal aortic aneurysm (AAA).
  
  
  
  Wild-type 8-week-old C56BL/6 male mice (n = 120) were equally divided into three groups: (1) BAPN group: 0.2% 3-aminopropionitrile fumarate salt (BAPN) drinking water was provided to mice 2 days before surgery until the end of study. Sham aneurysm induction surgery was performed using 5 μL of heat deactivated elastase. (2) Elastase group: mice were given regular drinking water without BAPN. During aneurysm induction surgery, 5 μL of the active form of elastase (10.3 mg protein/mL, 5.9 U/mg protein) was applied on top of the infrarenal abdominal aorta adventitia for 5 minutes. (3) BAPN+elastase group: mice were given BAPN drinking water and the active form of elastase application, as above. On postoperative days 7, 14, 21, 28, and 100, aortic samples were collected for histology, cytokine array, and gelatin zymography after aortic diameter measurement.
  
  
  
  Compared with the elastase group, the BAPN+elastase group had a higher AAA formation rate (93% vs 65%; P < .01) with more advanced AAAs (25 of 42 vs 1 of 40 for stage II and III; P < .001). Aneurysms from the BAPN+elastase group demonstrated persistent long-term growth (221.5% ± 36.6%, 285.8% ± 78.6%, and 801% ± 160% on days 21, 28, and 100, respectively; P < .001), with considerable thrombus formation (54%) and rupture (31%) at the advanced stages of AAA development. Cytokine levels (pro-matrix metalloproteinase 9, interleukin-1β, interleukin-6, chemokine [C-C motif] ligand 5, triggering receptor expressed on myeloid cells 1, monocyte chemotactic protein 1, and tissue inhibitor of metalloproteinase 1) in the BAPN+elastase group were higher than in the elastase group on day 7. After day 7, cytokine levels returned to baseline, with the exception of elevated matrix metalloproteinase 2 activity. By histology, CD3-positive T cells in the BAPN+elastase group were elevated on days 28 and 100.
  
  
  
  A combination of oral BAPN administration and periaortic elastase application induced a chronic, advanced-stage AAA with characteristics of persistent aneurysm growth, thrombus formation, and spontaneous rupture. Future studies should use this model, especially for examining tissue remodeling during the late stages of aneurysm development.
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Guanyi
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Gang
authors.initials: G
authors.lastname: Su
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: John P
authors.initials: JP
authors.lastname: Davis
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Basil
authors.initials: B
authors.lastname: Schaheen
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Emily
authors.initials: E
authors.lastname: Downs
authors.affiliation: Molecular Imaging Core, Department of Radiology, University of Virginia, Charlottesville, Va.
authors.forename: R Jack
authors.initials: RJ
authors.lastname: Roy
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va.
authors.forename: Gorav
authors.initials: G
authors.lastname: Ailawadi
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, Va. Electronic address: gru6n@virginia.edu.
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Upchurch
mesh_terms: D000629:Aminopropionitrile / Q000031:analogs & derivatives*; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D001019:Aortic Rupture / Q000139:chemically induced; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D018450:Disease Progression; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase; D013927:Thrombosis / Q000139:chemically induced; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C027243:beta-aminopropionitrile fumarate; D000629:Aminopropionitrile; D010196:Pancreatic Elastase