title: Murine abdominal aortic aneurysm model by orthotopic allograft transplantation of elastase-treated abdominal aorta.
abstract: OBJECTIVE
  Murine models have proved instrumental in studying various aspects of abdominal aortic aneurysm (AAA), from identification of underlying pathophysiologic changes to the development of novel therapeutic strategies. In the current study, we describe a new model in which an elastase-treated donor aorta is transplanted to a recipient mouse and allowed to progress to aneurysm. We hypothesized that by transplanting an elastase-treated abdominal aorta of one genotype to a recipient mouse of a different genotype, one can differentiate pathophysiologic factors that are intrinsic to the aortic wall from those stemming from circulation and other organs.
  
  
  METHODS
  Elastase-treated aorta was transplanted to the infrarenal abdominal aorta of recipient mice by end-to-side microsurgical anastomosis. Heat-inactivated elastase-treated aorta was used as a control. Syngeneic transplants were performed with use of 12-week-old C57BL/6 littermates. Transplant grafts were harvested from recipient mice on day 7 or day 14 after surgery. The aneurysm outcome was measured by aortic expansion, elastin degradation, proinflammatory cytokine expression, and inflammatory cell infiltration and compared with that produced with the established, conventional elastase infusion model.
  
  
  RESULTS
  The surgical technique success rate was 75.6%, and the 14-day survival rate was 51.1%. By day 14 after surgery, all of the elastase-treated transplanted abdominal aortas had dilated and progressed to AAAs, defined as 100% or more increase in the maximal external diameter compared with that measured before elastase perfusion, whereas none of the transplanted aortas pretreated with inactive elastase became aneurysmal (percentage increase in maximum aortic diameter: 159.36% ± 23.27%, transplanted elastase, vs 41.46% ± 9.34%, transplanted inactive elastase). Aneurysm parameters, including elastin degradation and infiltration of macrophages and T lymphocytes, were found to be identical to those observed in the conventional elastase model. Quantitative polymerase chain reaction analysis revealed similarly increased levels of proinflammatory cytokines (relative changes of mRNA in the conventional elastase model vs transplant model: tumor necrosis factor α, 1.71 ± 0.27 vs 2.93 ± 0.86; monocyte chemoattractant protein 1, 2.36 ± 0.58 vs 2.87 ± 0.51; chemokine (C-C motif) ligand 5, 3.37 ± 0.92 vs 3.46 ± 0.83; and interferon γ, 3.09 ± 0.83 vs 5.30 ± 1.69). Using green fluorescent protein transgenic mice as donors or recipients, we demonstrated that a small quantity of mononuclear leukocytes in the transplant grafts bared the genotype of the donors.
  
  
  CONCLUSIONS
  Transplanted elastase-treated abdominal aorta could develop to aneurysm in recipient mice. This AAA transplant model can be used to examine how the microenvironment of a transplanted aneurysmal aorta may be altered by the contributions of the "global" environment of the recipient.
authors: Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisc.
authors: Zhenjie
authors: Z
authors: Liu
authors: Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisc.
authors: Qiwei
authors: Q
authors: Wang
authors: Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisc.
authors: Jun
authors: J
authors: Ren
authors: Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisc.
authors: Carmel Rebecca
authors: CR
authors: Assa
authors: Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisc.
authors: Stephanie
authors: S
authors: Morgan
authors: Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisc.
authors: Jasmine
authors: J
authors: Giles
authors: Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisc.
authors: Qi
authors: Q
authors: Han
authors: Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisc. Electronic address: liub@surgery.wisc.edu.
authors: Bo
authors: B
authors: Liu
mesh_terms: D064591:Allografts; D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology / Q000637:transplantation*; D017544:Aortic Aneurysm, Abdominal / Q000503:physiopathology* / Q000601:surgery*; D060833:Cellular Microenvironment; D004195:Disease Models, Animal; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010196:Pancreatic Elastase / Q000494:pharmacology
chemical_list: D010196:Pancreatic Elastase