L-arginine attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells

ObjectiveEndothelial dysfunction is a key event in the onset and progression of atherosclerosis associated with diabetes. Increasing cell senescence may lead to endothelial dysfunction and contribute to vascular complications. Therefore, we aimed to elucidate the possible role and mechanism of L-arginine in preventing cell senescence induced by high glucose.MethodsHUVECs were respectively cultured under normal control glucose (5.5 mM), high glucose (33 mM), co-incubation with L-arginine (800 μM)and high glucose, and senescence was identified by β-galactosidase staining, change of cell cycle and telomerase activity. Akt and eNOS activity was analyzed by western blot.ResultsHigh glucose significantly increased number of β-galactosidase-positive stained cells, inhibited telomerase activity, increased proportion of cells in the G0/G1 phase and reduced proportion in the S phase, and decreased NO synthesis. L-arginine significantly attenuated these senescent alterations. Furthermore, high glucose induced a decrease in Akt and eNOS activity, and L-arginine prevented the decrease in activity. The PI3K inhibitor LY294002 or eNOS inhibitor L-NAME attenuated anti-senescence effect of L-arginine.ConclusionL-arginine may have an anti-senescence effect via the PI3K/Akt pathway in HUVECs exposed to high glucose and it might be a therapeutic agent for diabetic vascular complications.