The mechanism of vascular endothelial cell damage by urate

Objective To observe the role of different concentration of urate in the expression of vascular endothelial cell injury associated factors;To identify the mechanism of injury of hyperuricemia on vascular endothelial cells.Methods All experiments were performed with human vascular endothelial cells cultured and endothelial cells and monocytes co-cultured in vitro.As stimulations,the concentration of urate in culture medium were 6.6mg/dl(which was the minimum of average uric acid in human),and double,triple,four times,five times of this concentration,respectively.Different concentrations of urate were used to stimulate vascular endothelial cells for 48 hours.The levels of IL-1、TNF-α、ICAM-1 and PAI-1 in the supernatants of cell cultures were measured by enzyme linked immunosorbent assay(ELISA).Meanwhile,the expression of hUAT (human urate transporer) mRNA was tested by using RT-PCR.Results ①different concentration of urate cultured with vascular endothelial cells:the expressions of IL-1、 TNF-α、ICAM-1 and PAI-1 significantly increased in high concentration of urate groups compared with the control group(P0.05);②different concentration of urate co-cultured with vascular endothelial cells and monocytes:the expressions of IL-1、TNF-α 、ICAM-1 and PAI-1 were progressively increased in high concentration of urate groups,significantly higher than the control group(P0.05);③the expression of hUAT mRNA in high concentration of urate group was significantly lower than that of the control group(P0.05),while it significantly progressively decreased in co-cultured groups(P0.05).Conclusions Urate can cause direct injury on endothelial cells as an independent risk factor,mononuclear cells also play an important role in the process of endothelial cell injury,and endothelial cells and monocytes co-cultured cause more progressive injury on endothelial cells.