New ascending aortic aneurysm model in rats reproduces main structural features of degenerative ascending thoracic aortic aneurysms in human beings

ObjectivesThe singularity of the ascending aorta regarding mechanisms driving aneurysm formation requires the development of specific animal models. We investigated if adventitial elastase application results in ascending aorta aneurysms in rats.MethodsAdult Lewis rats (n = 26) were anesthetized, their ascending aortas measured by transthoracic ultrasound, and exposed via median sternotomy. Elastase or saline was applied on the ascending aortic adventitia. Ascending aorta diameters were monitored by ultrasound at 10 and 30 days, when the animals were killed. Wall area was measured on orcein stained sections. Matrix metalloproteinase-2 and matrix metalloproteinase-9 levels were quantified on gelatin zymography.ResultsFollowing elastase application, ascending aortic diameter increased at 10 and 30 days follow-up by 38% and 44%, respectively (P = .004). Despite thinning of the media secondary to vascular dilation, standardized medial area was not different between elastase-treated aortas and controls. Standardized total wall area had a significant increase in treated aortas compared with controls. Active matrix metalloproteinase-2 was significantly increased at 30 days in treated aortas, whereas active matrix metalloproteinase-9 was no different from controls.ConclusionsElastase application on rat ascending aortic adventitia produced aneurysms, creating a reproducible model. Aortic wall remodeling evolved toward an increase in total wall area, reproducing the main structural features of this disease in human beings. The singularity of the ascending aorta regarding mechanisms driving aneurysm formation requires the development of specific animal models. We investigated if adventitial elastase application results in ascending aorta aneurysms in rats. Adult Lewis rats (n = 26) were anesthetized, their ascending aortas measured by transthoracic ultrasound, and exposed via median sternotomy. Elastase or saline was applied on the ascending aortic adventitia. Ascending aorta diameters were monitored by ultrasound at 10 and 30 days, when the animals were killed. Wall area was measured on orcein stained sections. Matrix metalloproteinase-2 and matrix metalloproteinase-9 levels were quantified on gelatin zymography. Following elastase application, ascending aortic diameter increased at 10 and 30 days follow-up by 38% and 44%, respectively (P = .004). Despite thinning of the media secondary to vascular dilation, standardized medial area was not different between elastase-treated aortas and controls. Standardized total wall area had a significant increase in treated aortas compared with controls. Active matrix metalloproteinase-2 was significantly increased at 30 days in treated aortas, whereas active matrix metalloproteinase-9 was no different from controls. Elastase application on rat ascending aortic adventitia produced aneurysms, creating a reproducible model. Aortic wall remodeling evolved toward an increase in total wall area, reproducing the main structural features of this disease in human beings.