Role of Aortic Cell Heterogeneity in Aneurysm & Dissection (J. Cooke, MD and guests) March 14, 2022

This session explores how embryologic cell origin within the aortic wall may influence susceptibility to thoracic aortic aneurysm and dissection. Using mouse models, the speakers review how second heart field–derived cells and cardiac neural crest–derived cells occupy distinct regions of the proximal aorta, with pathology localizing preferentially to second heart field territory. Angiotensin II infusion and lineage-tracing studies showed medial thickening and outer wall injury in this region, prompting single-cell RNA sequencing of second heart field–derived cells. A distinct fibroblast subpopulation demonstrated downregulation of extracellular matrix genes and TGF-β signaling components, suggesting impaired wall maintenance. Conditional deletion of TGF-β receptor 2 or LRP1 in second heart field cells further supported a critical protective role for this lineage. The discussion highlights how cellular heterogeneity may explain regional vulnerability in thoracic aortic disease. KEY LEARNING CONCEPTS • The proximal thoracic aorta contains smooth muscle and stromal cells derived from distinct embryologic origins, primarily cardiac neural crest and second heart field • Thoracic aortic pathology in experimental models localizes predominantly to the outer medial layers, corresponding to second heart field–derived regions • Single-cell RNA sequencing identified a fibroblast subpopulation with reduced extracellular matrix and TGF-β pathway gene expression after angiotensin II infusion • Deletion of TGF-β receptor 2 or LRP1 in second heart field derived cells worsens aortic pathology, supporting a protective role for this lineage • Aortic cell heterogeneity may help explain why aneurysm and dissection develop in specific regions rather than uniformly throughout the aorta FOR MORE INFORMATION HM Academic Institute: https://www.houstonmethodist.org/acad... For the latest education and training opportunities from DeBakey CV Education: http://bit.ly/HMdebakeyemail Follow Us: DeBakey CV Education Homepage https://www.houstonmethodist.org/acad... DeBakey CV Education Facebook   / about   DeBakey CV Education X https://x.com/DeBakeyCVedu/ DeBakey CV Education LinkedIn   / debakey-cv-education   DeBakey CV Edu Instagram   / debakeycvedu   Want concise, relevant reviews of the hottest topics in CV medicine? Subscribe for FREE to the Methodist DeBakey Cardiovascular Journal for quarterly, peer-reviewed issues delivered to your door. https://journal.houstonmethodist.org/