Pyoverdine-induced iron dysregulation exacerbates vascular endothelial barrier dysfunction under hyperglycemic conditions

assays demonstrated that PVD exposure reduced cell viability, triggered reactive oxygen species (ROS) bursts, and induced a loss of mitochondrial membrane potential. Ultrastructural observations via transmission electron microscopy confirmed pathological changes, including mitochondrial swelling, cristae disorganization, and cytoplasmic vacuolation. Functional assessments showed that PVD significantly increased the transendothelial flux of FITC-dextran and downregulated the expression of the tight junction proteins ZO-1 and Claudin-5, indicating compromised barrier integrity. Notably, these deleterious effects-including oxidative stress, mitochondrial damage, and barrier dysfunction-were significantly exacerbated under HG conditions. Collectively, our findings suggest that PVD impairs the vascular endothelial barrier by disrupting eukaryotic iron homeostasis and activating oxidative stress, leading to the downregulation of junctional proteins. This study identifies PVD as a key mediator of vascular injury in DFI and provides a theoretical rationale for targeting iron metabolism and oxidative stress as a therapeutic strategy.