Endothelial mechanosensitive transcription factor BHLHE40 induced by Piezo1 suppresses endothelial ferroptosis and inflammation via SLC7A11.

ABSTRACT: Endothelial dysfunction-driven vascular inflammation underlies sepsis and atherosclerosis. Piezo1 serves as a central mediator for endothelial mechanotransduction and inflammatory homeostasis. Nevertheless, the transcriptional pathways linking mechanical sensing to anti-inflammatory protection and the exact composition of its downstream signaling cascade remain incompletely resolved. Here, we identify BHLHE40 as an endothelial mechanosensitive transcription factor induced by Piezo1 that coordinates ferroptosis resistance and inflammation suppression. Mechanistically, shear stress activates Piezo1, triggering Ca²⁺ influx and calcineurin-dependent NFAT2 nuclear translocation. NFAT2 recruits HDAC1 to form a transcriptional complex that directly drives BHLHE40 expression. BHLHE40 then binds th

SUBMITTER: Miao S 

PROVIDER: S-EPMC12830637 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature