ETD

• endothelial nitric oxide synthase
• galectin-3-biding protein
• HFpEF

Galectin-3-binding protein (LGALS3BP) is a multifunctional glycoprotein involved in extracellular matrix remodeling, cell adhesion, and inflammation. Proteomic data from patients with heart failure with preserved ejection fraction (HFpEF) identified LGALS3BP among differentially expressed proteins and suggested activation of inflammatory pathways. Since endothelial nitric oxide synthase (eNOS) may influence endothelial responses to metabolic stress, this study investigated whether eNOS deletion affects LGALS3BP expression and isoform distribution. Wild-type (WT) and eNOS knockout (KO) murine aortic endothelial cells were exposed for 24 h to basal glucose, high glucose, high insulin, or their combination. Protein expression was assessed by Western blot. In WT cells, full-length LGALS3BP increased under high glucose and high insulin, with the strongest induction after combined treatment. In KO cells, full-length LGALS3BP showed only moderate changes, whereas the truncated isoform increased consistently under all metabolic stress conditions. Moreover, VCAM-1 expression was markedly increased in KO cells, indicating enhanced endothelial activation. These findings suggest that eNOS deficiency shifts LGALS3BP expression from the full-length to the truncated isoform and promotes an inflammatory endothelial phenotype under metabolic stress. Further studies are needed to clarify the role of LGALS3BP isoforms and their potential relevance in vascular dysfunction associated with HFpEF.