Abstract 17810: Second Heart Field-Derived Smooth Muscle Cells Contribute to Angiotensin II-Induced Medial Thickness in the Ascending Aorta
Objective: Smooth muscle cells (SMCs) in the ascending aorta are reported to be derived from two different embryonic origins, cardiac neural crest (CNC) and second heart field (SHF). Although previous studies have shown the location of CNC- and SHF-derived SMCs in embryonic or juvenile aortas, the distribution of these cells in the adult aorta is still unclear. During angiotensin II (AngII)-infusion, medial pathologies are most pronounced on the adventitial aspect of the outer curvature in the ascending aorta. The aim of this study was to delineate the distribution of these cell origins in the adult ascending aorta and to investigate the influence of AngII on these lineages.
Methods and Results: To map SMCs of CNC and SHF origin, ROSA26 lacZ mice were bred to transgenic mice containing Cre under control of a Wnt1 or Mef2c promotor, respectively. Whole aortas stained for β-galactosidase revealed differences in distribution of CNC and SHF-derived SMCs. The former SMCs were present from the aortic root and extended to the end of the aortic arch; while the later ended earlier just proximal of the innominate artery. To assess medial distribution of these cells, both sagittal and cross sections were obtained. CNC-derived SMCs were detected in the inner aspect of the outer curvature and transmedial in the inner curvature. On the other hand, SHF-derived SMCs were detected in the outer laminar layers of the ascending aorta. We subsequently determined whether these cell lineages were influenced during AngII infusion. After 28 days of AngII infusion, medial thickness predominantly occurred in the outer aspect of the ascending aorta which co-localizes with the site of SHF-derived SMCs.
Conclusion: The ascending aorta has an inner medial layer of CNC-derived SMCs covered by an outer sleeve of SHF-derived SMCs. These SHF-derived SMCs populate areas of AngII-induced medial thickening in the ascending aorta.
Author Disclosures: H. Sawada: None. J.J. Moorleghen: None. D.L. Rateri: None. M.W. Majesky: None. A. Daugherty: None.
- © 2016 by American Heart Association, Inc.