TY - GEN
T1 - Pathophysiology of abdominal aortic aneurysms
T2 - Insights from the elastase-induced model in mice with different genetic backgrounds
AU - Thompson, Robert W.
AU - Curci, John A.
AU - Ennis, Terri L.
AU - Mao, Dongli
AU - Pagano, Monica B.
AU - Pham, Christine T.N.
PY - 2006/11
Y1 - 2006/11
N2 - 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 newavenues 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.
AB - 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 newavenues 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.
KW - Abdominal aortic aneurysm
KW - Animal models of disease
KW - Cytokines
KW - Elastase
KW - Extracellular matrix
KW - Genetic susceptibility
KW - Genetically altered mice
KW - Inflammation
KW - Proteinases
UR - http://www.scopus.com/inward/record.url?scp=34249319574&partnerID=8YFLogxK
U2 - 10.1196/annals.1383.029
DO - 10.1196/annals.1383.029
M3 - Conference contribution
C2 - 17182923
AN - SCOPUS:34249319574
SN - 1573316571
SN - 9781573316576
T3 - Annals of the New York Academy of Sciences
SP - 59
EP - 73
BT - The Abdominal Aortic Aneurysm
PB - Blackwell Publishing Inc.
ER -