Abstract 16640: Foxo1 Impairs Whereas Statin Protects Endothelial Function in Hyperglycemic Conditions Through Reciprocal Regulation of Kruppel-like Factor 2

TL;DRAbstract

Endothelial dysfunction is an initial critical factor in the pathogenesis of diabetic vascular complications. Krüppel-like factor 2 ( KLF2) is implicated as a key molecule maintaining endothelial function. We investigated the role of a forkhead transcription factor, FOXO1, and HMG-CoA reductase inhibitor in KLF2 regulation in hyperglycemic conditions. FOXO1 expression was increased by 190% (p<0.05), whereas KLF2 and eNOS expression were decreased by 60% (p<0.05) and by 70% (p<0.05) in human umbilical vein endothelial cells incubated in 30 mM glucose for 24 h, all of which were completely reversed by FOXO1 siRNA. Adenovirus-mediated overexpression of FOXO1 decreased the expression of KLF2 and eNOS by 49% and 69% (p<0.05). Atorvastatin (1 μM) inhibited FOXO1 not only by increasing phosphorylation by 170% (p<0.05) but also by degrading FOXO1 protein by 70% (p<0.05). Atorvastatin also restored KLF2 expression suppressed in high glucose conditions similar to the control l

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