β-aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Young Mice

Abstract

ABSTRACTThis study characterized β-aminopropionitrile (BAPN)-induced aortopathies in young mice. The effects of BAPN were first determined with regard to BAPN dose and mouse strain, age, and sex. BAPN-induced aortic rupture predominantly occurred or originated in the descending thoracic aorta. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while there were more heterogeneous changes in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissections with false lumen formation, macrophage infiltration, collagen deposition, and remodeling of the wall surrounding the false lumen. Cells surrounding the false lumen were predominantly positive for α-smooth muscle actin. To investigate the molecular basis of the regional heterogeneity, ascending and descending thoracic aortas were harvested after one week of BAPN administration prior to the appearance of overt pathology. BAPN compromised contractile properties in both regions equivalently, and RNA sequencing did not show obvious differences between the two aortic regions in smooth muscle cell markers, cell proliferation markers, and extracellular components. In conclusion, BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in young mice.