Dapagliflozin improves the dysfunction of human umbilical vein endothelial cells (HUVECs) by downregulating high glucose/high fat-induced autophagy through inhibiting SGLT-2

Objective

To investigate the effect of Dapagliflozin (Da) on the disorders of human umbilical vein endothelial cells (HUVECs) induced by high glucose and high fat (HG/HF).

Methods

Immunohistochemistry and immunofluorescence were used to detect the SGLT-2 expression in thoracic aortic tissues. After transfected with overexpressed plasmid SLC5A2, autophagy and cell functions of HUVECs were detected with the treatment of autophagy inhibitor 3-MA (5 mM). HUVECs were exposed to mannitol (MAN), glucose/palmitate (Hg/PA), and Hg/PA/Da for 24 h, and the proliferation of HUVECs was detected by CCK-8. The protein expression levels, endothelial cell functions (cell proliferation, migration, tubular formation, apoptosis, and autophagy) in endothelial cells were evaluated.

Results

The SGLT-2 expression was found in atherosclerotic human thoracic aorta tissues and HG/PA induced HUVECs (P < 0.05). After the overexpression of SGLT-2 in HUVECs, the proliferation, migration and tubule formation ability of HUVECs were inhibited, and autophagy and apoptosis were increased, which were reversed by 3-MA (P < 0.05). After the addition of Sodium-glucose co-transporters 2 inhibitor, Dapagliflozin, the proliferation of HUVECs, the tubule formation, autophagy, apoptosis and migration ability of cells inhibited by HG/PA were significantly improved (P < 0.05). Moreover, the increased protein expression levels of autophagy and apoptosis in HG/PA induced HUVECs were also decreased by the treatment of Dapagliflozin (P < 0.05).

Conclusions

Dapagliflozin can improve the dysfunction of high glucose/high fat-induced human umbilical vein endothelial cells by downregulate autophagy through inhibiting SGLT-2.