Animal Models of Aneurysms

Dobrin, Philip B.

doi:10.1007/s100169900315

Cited by 38 publications

(28 citation statements)

References 83 publications

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“…For example, the elastase-induced murine model of AAAs is dependent on an initial aortic wall injury with pancreatic elastase, an enzyme not known or suspected to play a role in human aneurysms. 48 Secondly, this model does not depend on the presence of atherosclerosis, intrinsic defects in structural matrix proteins or hypertension, each of which has been implicated in at least some forms of human AAAs, and elastase-induced aneurysms in rodents only rarely undergo spontaneous rupture. 1 Despite these reservations, the elastaseinduced model has been useful to examine biological mechanisms underlying AAAs because the inciting injury does not result in immediate destruction of medial elastic fibers or …”

Section: Discussionmentioning

confidence: 99%

Experimental Abdominal Aortic Aneurysms in Mice Lacking Expression of Inducible Nitric Oxide Synthase

Lee

Borhani

Ennis

et al. 2001

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Abstract-To determine if nitric oxide synthase (NOS) contributes to the pathophysiology of abdominal aortic aneurysms (AAAs), C57BL/6J mice underwent transient aortic injury to induce a chronic inflammatory response. Wild-type mice developed a significant increase in aortic diameter within 14 days of elastase perfusion (115Ϯ16%, 40% incidence of AAAs), along with intense and widespread staining for nitrotyrosine, mononuclear inflammation, and delayed destruction of the elastic lamellae. Expression of both endothelial and neuronal forms of NOS was substantially decreased within AAAs, whereas inducible NOS (iNOS) mRNA was increased 360%, and the enzyme was localized to infiltrating inflammatory cells. By using mice with targeted deletion of iNOS to evaluate the functional importance of this enzyme, male iNOS -/-mice developed the same extent of aneurysmal dilatation as congenic controls (121Ϯ22%, 40% incidence of AAAs) and exhibited similar structural features except for diminished nitrotyrosine staining. Aneurysmal dilatation was actually enhanced in female iNOS -/-mice (141Ϯ16%, 80% incidence of AAAs; PϽ0.05), but this effect was reversed by previous oophorectomy. Although extensive protein nitration and increased expression of iNOS accompany the development of elastase-induced experimental AAAs, iNOS is not required in this process and its absence may be deleterious.

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Section: Discussionmentioning

confidence: 99%

Experimental Abdominal Aortic Aneurysms in Mice Lacking Expression of Inducible Nitric Oxide Synthase

Lee

Borhani

Ennis

et al. 2001

ATVB

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“…Studies using animal models have led to important insights into the cellular and molecular events underlying aneurysmal degeneration (12). Many of these studies have involved an elastase-induced rat model of AAAs, in which a chronic aortic wall inflammatory response is associated with progressive elastic fiber degradation and aneurysmal dilatation (13,14).…”

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Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms

et al. 2000

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“…Several models of AAAs that have been created in large animals have been reviewed recently. 3,4 In the current review, we focus on recent advances in the development of models of AAA in mice (Table). Mice have become dominant in biomedical research for reasons that include their small size, their relative cheapness, the ability to compare well-documented genetic backgrounds, and the ability to delete or overexpress specific genes.…”

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confidence: 99%

Mouse Models of Abdominal Aortic Aneurysms

Daugherty

Cassis

2004

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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.

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Animal Models of Aneurysms

Cited by 38 publications

References 83 publications

Experimental Abdominal Aortic Aneurysms in Mice Lacking Expression of Inducible Nitric Oxide Synthase

Experimental Abdominal Aortic Aneurysms in Mice Lacking Expression of Inducible Nitric Oxide Synthase

Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms

Mouse Models of Abdominal Aortic Aneurysms

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