Abstract 254: Cellular Heterogeneity of the Ascending Aorta Relationship to AngII-Induced Medial Hemorrhage

Abstract

Introduction and Objective: Infusion of angiotensin II (AngII) into mice generates pronounced aneurysms that are localized to the ascending aorta. Following prolonged infusion of AngII, the resulting ascending aneurysms are characterized by pronounced lumen dilation and concentric medial thickening with progressive expansion between elastin layers from the lumen to the adventitia of the aorta. The presence of medial hemorrhage is a common characteristic within 5 days of initiating AngII infusion. The purpose of this study was to determine whether the location of medial hemorrhage coincided with overt structural or cellular transition within the aorta. Methods and Results: Eight-week-old, male, C57BL/6 mice were fed a normal laboratory diet and infused with either saline (N=5) or AngII (1,000 ng/kg/min, N=20) subcutaneously using osmotic mini pumps for 5 days. Mice were terminated after 5 days of AngII infusion. Thirty percent (6 out of 20) displayed hemorrhage, visible from the ascending aorta to the aortic arch. Serial sections (10 μm) were acquired through the entire aortic root and ascending aorta. Alpha-actin and reticular fibroblast (ER-TR7) antibodies detected the location of smooth muscle cells (SMC) and fibroblasts, respectively. In both groups, there was a transition within the aortic root in which the media no longer immunostained positively for alpha actin. Conversely, this region immunostained positively for fibroblasts. Hemorrhages occurred distal to the cellular phenotypic changes seen in the aortic root. Conclusion: These findings suggest that the development of AngII-induced medial hemorrhage within the ascending aorta did not correspond to the medial cellular transitions present in the aortic root.