title: Extra- and Intraluminal Elastase Induce Morphologically Distinct Abdominal Aortic Aneurysms in Mice and Thus Represent Specific Subtypes of Human Disease.
abstract: Topical application of elastase to induce arterial aneurysm formation is an emerging murine model of vascular disease. In the context of aortic abdominal aneurysm (AAA), angiotensin II infusion and porcine pancreatic elastase perfusion models are commonly used today. This study, therefore, compares matrix remodeling, inflammation, and angiogenesis as distinct features of aneurysms in two models treated with intra-/extraluminal elastase. C57BL/6 mice underwent intra-/extraluminal elastase application via laparotomy and were followed up for 4 weeks. Basic histology and immunohistochemistry were performed at different time points along with transmission electron microscopy, PCR analysis, TUNEL assays, and blood analysis. Both models did not differ in aneurysm growth rate, but they showed distinct features and results depending on the way of elastase application. Extraluminal aneurysm induction preserved endothelial cell function and elastic fibers but showed ongoing acute inflammation, mainly in the adventitia. The destruction of elastic layers followed by chronic inflammation was a characteristic of intraluminal elastase perfusion, as well as medial angiogenesis, a key feature in human AAA. Different animal models harbor different features of human AAA and must, therefore, be chosen wisely. External elastase application mimics an acute inflammatory aneurysm, whereas intraluminal elastase perfusion shows chronic inflammation with angiogenesis and endothelial destruction, thus better mimicking human disease.
authors.affiliation: Department of General, Visceral, Vascular, and Pediatric Surgery, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Busch
authors.forename: Amina
authors.initials: A
authors.lastname: Holm
authors.forename: Nicole
authors.initials: N
authors.lastname: Wagner
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
authors.forename: Mathias
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: Christoph
authors.initials: C
authors.lastname: Otto
authors.forename: Johannes
authors.initials: J
authors.lastname: Baur
authors.forename: Richard
authors.initials: R
authors.lastname: Kellersmann
authors.forename: Udo
authors.initials: U
authors.lastname: Lorenz
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D010196:Pancreatic Elastase; D010641:Phenotype; D059748:Proteolysis; D013997:Time Factors
chemical_list: D010196:Pancreatic Elastase