FOXO1-Driven Endothelial Senescence in Bicuspid Aortic Valve-Associated Thoracic Aortic Aneurysm

Endothelial cell senescence is a hallmark of endothelial dysfunction, yet direct evidence linking endothelial senescence to BAV-TAA has not been established. In this study, we generated induced pluripotent stem cells (iPSCs) from both BAV-TAA patients and healthy controls, subsequently differentiating them into endothelial cells (iECs).

Our findings revealed that BAV-TAA-iECs exhibited senescence phenotype, including impaired proliferation, diminished migratory capacity, upregulated senescence markers (p53, p21, p16), and a pronounced senescence-associated secretory phenotype (SASP). Transcriptomic analysis through RNA sequencing indicated aberrant activation of the FOXO signaling pathway in BAV-TAA-iECs which might contribute to BAV-TAA-iEC senescence.