DPP-4 inhibition protects human umbilical vein endothelial cells from hypoxia-induced vascular barrier impairment

Dipeptidyl peptidase-4 (dpp-4) inhibitors are relatively new class of anti-diabetic drugs. some protective effects of dpp-4 on cardiovascular disease have been described independently from glucose-lowering effect. however,the detailed mechanisms by which dpp-4 inhibitors exert on endothelial cells remain elusive. the purpose of this research was to determine the effects of dpp-4 inhibitor on endothelial barrier function. human umbilical vein endothelial cells (huvecs) were cultured and exposed to hypoxia in the presence or absence of diprotin a,a dpp-4 inhibitor. immunocytochemistry of vascular endothelial (ve-) cadherin showed that jagged ve-cadherin staining pattern induced by hypoxia was restored by treatment with diprotin a. the increased level of cleaved β-catenin in response to hypoxia was significantly attenuated by diprotin a,suggesting that dpp-4 inhibition protects endothelial adherens junctions from hypoxia. subsequently,we found that diprotin a inhibited hypoxia-induced translocation of nf-κb from cytoplasm to nucleus through decreasing tnf-α expression level. furthermore,the tube formation assay showed that diprotin a significantly restored hypoxia-induced decrease in number of tubes by huvecs. these results suggest that dpp-4 inhibitior protects huvecs from hypoxia-induced barrier impairment. © 2017 the authors