Pathophysiology of abdominal aortic aneurysms: insights from the elastase-induced model in mice with different genetic backgrounds.
Abdominal aortic aneurysms (AAAs) represent a complex degenerative disorder involving chronic aortic wall inflammation and destructive remodeling of structural connective tissue. Studies using human AAA tissues have helped identify a variety of molecular mediators and matrix-degrading proteinases, which contribute to aneurysm disease, thereby providing a sound foundation for understanding AAAs; however, these human tissue specimens represent only the "end stage" of a long and progressive disease process. Further progress in understanding the pathophysiology of AAAs is therefore dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. Based on original studies in rats, transient perfusion of the abdominal aorta with porcine pancreatic elastase has provided a reproducible and robust model of AAAs. More recent applications of this model to mice have also opened new avenues for investigation. In this review, we summarize investigations using the elastase-induced mouse model of AAAs including results in animals with targeted deletion of specific genes and more general differences in mice on different genetic backgrounds. These studies have helped us identify genes that are essential to the development of AAAs (such as MMP9, IL6, and AT1R) and to reveal other genes that may be dispensable in aneurysm formation. Investigations on mice from different genetic backgrounds are also beginning to offer a novel approach to evaluate the genetic basis for susceptibility to aneurysm development.
Thompson
Robert W
RW
Department of Surgery (Section of Vascular Surgery), Washington University School of Medicine, St. Louis, Missouri 63110, USA. thompson@wudosis.wustl.edu
Curci
John A
JA
Ennis
Terri L
TL
Mao
Dongli
D
Pagano
Monica B
MB
Pham
Christine T N
CT
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D051379:Mice; D010196:Pancreatic Elastase / Q000378:metabolism*; D010477:Perfusion
D010196:Pancreatic Elastase