Single-cell RNA sequencing reveals endothelial cell heterogeneity and Sox18-mediated EndMT in abdominal aortic aneurysm

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Rationale: Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease lacking clinical predictors and effective pharmacologic therapies. The cellular heterogeneity and molecular changes of different cell types during AAA have been revealed in human and mouse aortas by single-cell RNA sequencing (scRNA-seq) technology. However, the heterogeneity and plasticity of endothelial cells (ECs) in AAA remain poorly characterized. Methods: scRNA-seq was performed on the abdominal aorta from angiotensin II (AngⅡ) and salt-induced AAA mice. Additionally, public scRNA-seq data of human and mouse AAA were analyzed with a focus on ECs. Cellular and animal experiments were conducted to validate EC heterogeneity and to investigate the role of SRY (sex-determining region on the Y chromosome)-box transcription factor 18 (Sox18) in endothelial-to-mesenchymal transition (EndMT) during AAA formation. Results: Unbiased clustering analysis identified 20 clusters encompassing 11 cell types. Four subpopulations of ECs were identified in AngⅡ and salt-induced mouse AAA models: Cd36 + lipid-handling ECs, Fn1 + mesenchymal-like ECs, Lrg1 + pleiotropically activated ECs, and Mmrn1 + lymphatic-like ECs. Similar results were observed in human AAA scRNA-seq data. Endothelial dysfunction and EndMT were detected at single cell solution and validated experimentally. Sox18 was identified as a pot

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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