4.4 Article

Abdominal aortic aneurysms: fresh insights from a novel animal model of the disease

Journal

VASCULAR MEDICINE
Volume 7, Issue 1, Pages 45-54

Publisher

ARNOLD, HODDER HEADLINE PLC
DOI: 10.1191/1358863x02vm413ra

Keywords

aneurysms; angiotensin; atherosclerosis; hyperlipidemia; inflammation

Funding

  1. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL062846] Funding Source: NIH RePORTER
  2. NHLBI NIH HHS [HL 62846] Funding Source: Medline

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Abdominal aortic aneurysms (AAA) have a high prevalence in aged populations and are responsible for a large number of deaths. Despite the widespread nature of the disease, relatively little is known regarding mechanisms for formation and progression of aortic aneurysms. In part, this lack of knowledge is attributable to a paucity of animal models for this disease. This review summarizes the available animal models of AAA and focuses on a novel model of reproducible AAA generated by infusion of angiotensin II (Ang II) into mice rendered hyperlipidemic by the absence of either apolipoprotein E or low-density lipoprotein receptors. AAA generated by AngII infusion have many characteristics of the human disease including marked luminal expansions, perimedial remodeling, inflammation, thrombosis and a link to hyperlipidemia. As in the human disease, male mice are more susceptible to the development of AAA than females. The vascular pathology occurs from the effects of AngII at AT1 receptors present on bone marrow-derived cells. Studies are ongoing to define the mediators responsible for AngII-induced inflammation and degradation of the medial layer of the vascular wall. The AngII-induced model of AAA has the potential to provide novel insights into the underlying mechanisms of this disease and assist with the development of pharmacological therapies.

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