Insights into ascending aortic aneurysm pathogenesis using in vivo and ex vivo imaging systems in angiotensin II-infused mice

Mary B. Sheppard, Alan Daugherty, Hong Lu


Thoracic aortic diseases, primarily ascending aortic aneurysms and dissection, are devastating clinical conditions with high risk of death. Genetic disorders are a common etiology of ascending aortic aneurysms and dissection (1). Although there are multiple genetic disruptions that lead to ascending aortic aneurysms and dissection, these diseases can be mimicked by manipulations in animal models. It is worth noting that angiotensin II (Ang II) and its type 1 (AT1) receptor activation contribute to the development and progression of ascending aortic pathologies in all of these animal models (2-7). Ascending aortic aneurysms are one risk factor for aortic dissection. A systematic review of published clinical investigations also provides evidence that aortic dissection is one cause of the progression of ascending aortic aneurysms (8), which is consistent with what has been reported in ascending aortic aneurysms induced by Ang II infusion in mice (9). This mouse model has several distinct aortic pathological features: (I) early time point intramural hematoma that is most apparent in the outer medial layers; (II) rapid and progressive luminal dilation; (III) elastin fragmentation; (IV) aortic wall thickening; (V) and penetrating ulcers. Consistent with the human disease, Ang II-induced ascending aortic aneurysms are not associated with hypercholesterolemia (9), whereas hypercholesterolemia augments Ang II-induced abdominal aortic aneurysms (10). This mouse model has provided insights into understanding associations between aortic dissection and ascending aortic aneurysms (9,11,12).

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