Postdoctoral Fellowship for Sawada: The Impact of Smooth Muscle Cell Embryonic Origin on TGF-beta Signaling during Thoracic Aortic Aneurysm Formation

This proposal focuses on embryonic origin of smooth muscle cells (SMCs) and TGF-â signaling in the pathophysiology of thoracic aortic aneurysm (TAA). TGF-â signaling is important for aortic wall integrity and activated through TGF-â type 2 receptors (TGFBR2). TGFBR2 depletion in SMCs causes spontaneous TAA formation with elastin fragmentation and medial thickening. Interestingly, these aortic pathologies were predominantly detected in the outer medial layers of the ascending aorta. SMCs in the media of the ascending aorta are derived from two different embryonic origins. Thus, we hypothesized that these pathological gradient is associated with heterogeneity of embryonic origin of SMCs. In this proposal, we will generate mice with TGFBR2 deletion in SMCs of selected embryonic origins and examine aortic pathologies and TGF-â signaling.