Roles of SIRT1 in High Glucose-induced Endothelial Impairment: Association with Diabetic Atherosclerosis

Background and Aims. We undertook this study to investigate the roles of SIRT1 in high glucose-induced endothelial impairment and their association with diabetic atherosclerosis. Methods. Otsuka Long-Evans Tokushima Fatty (OLETF) rats and nondiabetic rats of the same genetic background were included. Real-time PCR was used to detect SIRT1 mRNA expression in abdominal aorta at week 42. To further investigate the roles of SIRT1 on the function of endothelial cells in high glucose, human endothelial cells were treated with SIRT1 activator resveratrol for 24 h before being cultured in high glucose medium for 48 h. Results. Along with the early manifestation of atherosclerosis, SIRT1 mRNA level in OLETF group was significantly lower than that in control group (p <0.05). Compared with control cells, high glucose decreased nitric oxide (NO) secretion, but resveratrol treatment increased the expression of SIRT1 and the secretion of NO. After interfering with the expression of SIRT1 using SIRT1 siRNA, the effects of resveratrol on NO secretion were impaired. SIRT1 also counteracted the other pro-atherosclerotic effects of high glucose including the upregulating roles of high glucose on the expression of E-selectin mRNA and the downregulating roles of high glucose on the expression of endothelial nitric oxide synthase. Conclusions. Decreased expression of SIRT1 in artery may be involved in the initiation and development of diabetic atherosclerosis. Increasing SIRT1 expression may hold great promise in the prevention and therapy of atherosclerosis in diabetic patients. (C) 2011 IMSS. Published by Elsevier Inc.