Hypoxia-mediated SUMOylation of FADD exacerbates endothelial cell injury via the RIPK1-RIPK3-MLKL signaling axis.

ABSTRACT: Vascular endothelial cells are the predominant cell type in the cardiovascular system, and their dysfunction and death following hypoxic injury contribute to vascular lesions, playing an essential role in cardiovascular disease. Despite its importance, the mechanisms underlying vascular endothelial cell injury under hypoxia and potential therapeutic interventions remain poorly understood. Here, we constructed both an in vivo hypoxia model in C57BL/6 mice and an in vitro hypoxia model in HUVEC cells. Our findings demonstrated that hypoxia induces necroptosis in vascular endothelial cells and exacerbates inflammatory injury in vivo and in vitro, as evidenced by immunofluorescence and western blot. We identified FADD as a critical regulator of hypoxia-mediated necroptosis, with FADD knockdown

SUBMITTER: Yang L 

PROVIDER: S-EPMC11845712 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature