on January 22, 2004
Published online before print January 22, 2004, doi: 10.1161/01.ATV.0000118013.72016.ea
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Submitted on July 11, 2003
Accepted on January 8, 2004
Mouse Models of Abdominal Aortic Aneurysms
Alan Daugherty * and Lisa A. Cassis
From the Department of Medicine (A.D.), Graduate Center for Nutritional Sciences (A.D., L.A.C.), Department of Physiology (A.D.), and Division of Pharmaceutical Sciences (L.A.C.), University of Kentucky, Lexington.
* To whom correspondence should be addressed. E-mail: Alan.Daugherty{at}uky.edu.
Abstract--Many mouse models of abdominal aortic aneurysms have been developed that use a diverse array of methods for producing the disease, including genetic manipulation and chemical induction. These models could provide insight into potential mechanisms in the development of this disease. Although experimental studies on abdominal aortic aneurysms (AAAs) have used a variety of mammalian and avian approaches, there is an increasing reliance on the use of mice. The models recapitulate some facets of the human disease including medial degeneration, inflammation, thrombus formation, and rupture. Most of the mouse models of AAA are evoked either by genetically defined approaches or by chemical means. The genetic approaches are spontaneous and engineered mutations. These include defects in extracellular matrix maturation, increased degradation of elastin and collagen, aberrant cholesterol homeostasis, and enhanced production of angiotensin peptides. The chemical approaches include the intraluminal infusion of elastase, periaortic incubations of calcium chloride, and subcutaneous infusion of AngII. A common feature of these models is the reduction of AAA incidence and severity by the prophylactic administration of matrix metalloproteinase (MMP) inhibitors or genetically engineered deficiencies of specific members of this proteolytic protein family. The validation of mouse models of AAAs will provide insight into the mechanisms of progression of the human disease.
Key words: aneurysms • mice
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