S100A4-lineage cells contribute modestly to angiotensin II-mediated thoracic aortic aneurysms through angiotensin II type 1a receptor in mice

Authors

• Sohei Ito, University of Kentucky College of MedicineFollow
• Jeff Z. Chen, University of Kentucky College of MedicineFollow
• Deborah A. Howatt, University of Kentucky College of MedicineFollow
• Jessica J. Moorleghen, University of Kentucky College of MedicineFollow
• Hong S. Lu, University of KentuckyFollow
• Alan Daugherty, University of KentuckyFollow
• Hisashi Sawada, University of KentuckyFollow

Abstract

Angiotensin II (AngII) exerts a critical role in thoracic aortic aneurysm (TAA) formation via AngII type 1a receptor (AT1aR). However, the principal cell type mediating this process remains unclear. Our previous study demonstrated that S100A4-lineage cells are present in the aortic wall and involved in AngII-induced vascular remodeling. In the present study, we investigated whether S100A4-lineage cells contribute to AngII-mediated TAA formation through AT1aR. Proteomic, bulk RNA sequencing, and single-cell RNA sequencing data were analyzed to assess changes in S100A4 abundance in response to AngII infusion. Lineage tracing was performed to track S100A4-lineage cells during AngII-mediated TAA formation. Either saline or AngII was infused in mice with genetic deletion of AT1aR in S100A4-lineage cells and their wild-type littermates. AngII infusion increased S100A4 protein and mRNA abundance significantly in the ascending aorta, particularly within smooth muscle cells and fibroblasts. Lineage tracing revealed that S100A4-positive cells were localized to the media and adventitia under basal conditions. Following AngII infusion, S100A4-lineage cells expanded markedly throughout the entire aortic wall and comprised a heterogeneous population including smooth muscle cells and fibroblasts. Deletion of AT1aR in S100A4-lineage cells partially reduced AngII-induced TAA formation. In conclusion, S100A4-lineage cells modestly contribute to AngII-mediated TAA development through AT1aR in mice.

Document Type

Article

Publication Date

5-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 Ito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

10.1371/journal.pone.0348111

Archival?

Archival

Repository Citation

Ito, Sohei; Chen, Jeff Z.; Howatt, Deborah A.; Moorleghen, Jessica J.; Lu, Hong S.; Daugherty, Alan; and Sawada, Hisashi, "S100A4-lineage cells contribute modestly to angiotensin II-mediated thoracic aortic aneurysms through angiotensin II type 1a receptor in mice" (2026). Physiology Faculty Publications. 209.
https://uknowledge.uky.edu/physiology_facpub/209