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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.<\/jats:p>","DOI":"10.1371\/journal.pone.0348111","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:36:51Z","timestamp":1778607411000},"page":"e0348111","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["S100A4-lineage cells contribute modestly to angiotensin II-mediated thoracic aortic aneurysms through angiotensin II type 1a receptor in mice"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-2946","authenticated-orcid":true,"given":"Sohei","family":"Ito","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff Z.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah 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