Pathophysiology of abdominal aortic aneurysms: Insights from the elastase-induced model in mice with different genetic backgrounds

Robert W. Thompson, John A. Curci, Terri L. Ennis, Dongli Mao, Monica B. Pagano, Christine T.N. Pham

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

119 Scopus citations

Abstract

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.

Original languageEnglish
Title of host publicationThe Abdominal Aortic Aneurysm
Subtitle of host publicationGenetics, Pathophysiology, and Molecular Biology
PublisherBlackwell Publishing Inc.
Pages59-73
Number of pages15
ISBN (Print)1573316571, 9781573316576
DOIs
StatePublished - Nov 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1085
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Abdominal aortic aneurysm
  • Animal models of disease
  • Cytokines
  • Elastase
  • Extracellular matrix
  • Genetic susceptibility
  • Genetically altered mice
  • Inflammation
  • Proteinases

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