Experimental techniques and models in the study of the development and treatment of abdominal aortic aneurysm

Abstract

Treatment of rodent aortas with intraluminal elastase or periaortic calcium chloride creates reproducible aneurysms that have certain similarities to the human pathology; such aneurysms have been favoured in the investigation of the pathophysiology of aneurysm expansion. However, these models lack several of the prominent features of the human lesion, such as atherosclerosis and intraluminal thrombosis. The development of gene knockout mice may lead to a more analogous aneurysm formation, with associated atherosclerosis. Many large animal models have been used in the development of endovascular techniques but, in general, these do not mimic the human pathophysiology and fail to predict medium- and long-term complications.

Genetic Backgrounds but Not Sizes of Atherosclerotic Lesions Determine Medial Destruction in the Aortic Root of Apolipoprotein E–Deficient Mice

“…To induce aneurysms, CaCl 2 and thioglycolate have to be applied to the adventitia to enhance aortic wall inflammation. 34 Aortic aneurysms can be induced in B6.apoE -/-mice by angiotensin infusion, but in this model, aneurysms are independent of atherosclerotic lesions. 16 In contrast, C3H.apoE -/-mice develop spontaneous atheroscle- rosis and display disruption of the elastic lamellae and infiltration by macrophages, thus providing an experimental tool to study atherosclerotic aortic aneurysms.…”

“…Carrell et al 34 maintained that an ideal model of aortic aneurysms should include all of the pathologic features observed in the human condition, such as atherosclerosis, disruption of elastic lamellae in the tunica media, and adventitial inflammation. However, few animal models reproduce all of these features.…”

Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E–deficient mice

“…Aneurysms of the abdominal aorta represent a significant cardiovascular risk. Despite the common occurrence of this vascular disease, the mechanism(s) that leads to the pathology remains undefined (56). Aneurysms of the abdominal aorta have been demonstrated previously in apoE -/-mice (57,58).…”

Proteinases in cardiovascular aneurysms and rupture: targets for therapy?

“…Remarkably, genetic predisposition factors or criteria for identifying patients at risk for aortic or cardiac rupture remain largely undetermined. A better understanding of the mechanisms might allow these catastrophic events to be prevented, but the absence of reliable animal models has blocked progress in this field (7).…”