Smooth Muscle Cells and Fibroblasts in the Proximal Thoracic Aorta Exhibit Minor Differences Between Embryonic Origins in Angiotensin II-driven Transcriptional Alterations.

Background: Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the proximal region of the thoracic aorta being susceptible. Smooth muscle cells (SMCs) and selected fibroblasts in this region are derived from two embryonic origins: second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy formation, the contribution of CNC-derived cells remains unclear. Methods: Mef2c-Cre R26R Results: Short-term AngII infusion induced significant transcriptomic changes in both SHF- and nSHF-derived SMCs, but differences between origins were modest. Fibroblast transcriptomes also underwent notable changes by AngII infusion, but differences between SHF and nSHF origins remained modest. Interestingly, AngII infusion resulted in the emergence of a new fibroblast sub-population. Several molecules related to the extracellular matrix, such as Conclusion: Fibroblasts in the new subcluster exhibited lineage-specific differences in extracellular matrix-related genes; however, overall transcriptomic differences between origins in SMCs and fibroblasts in response to AngII were modest in the pre-pathological phase of AngII-induced thoracic aortopathy. GRAPHIC ABSTRACT: