Functional Role of Second Heart Field-derived Cells in Thoracic Aortopathies

The ascending aorta is a common location for thoracic aortopathies. Pathology predominates in the aortic media with disease severity being most apparent in outer laminar layers. In the ascending aorta, smooth muscle cells are derived from two different embryonic origins: cardiac neural crest and second heart field. Cells of these two origins have distinct distributions, and the localization of second heart field is coincident with the regional specificity of some forms of thoracic aortopathies. However, the role of second heart field-derived cells in the pathophysiology of thoracic aortopathies has been unclear. This study demonstrated a functional role of second heart field-derived smooth muscle cells using angiotensin II-induced aortopathy in mice. Unbiased proteomic analyses discerned potential roles of low density lipoprotein receptor-related protein 1 and TGF-β pathways on the aortic integrity. Functional ablation of either these pathways in cells derived from the second heart field augmented aortopathies including aneurysm and rupture in the ascending region. These results indicated a functional role of cells derived from the second heart field on the integrity of the aortic wall.