Correlation Of Uric Acid Vascular Endothelial Function In Pairs

BackgroundWhen modern people are exposed to western diet, the prevalence of hyperuricemia is increasing year by year. Epidemiological studies suggest that hyperuricemia is related with the cardiovascular diseases. The mechanism for direct causal relationship between hyperuricemia and cardiovascular events remains to be determined. The mechanism of hyperuricemia causing diseases is unclear, and endothelial dysfunction is thought to be an important factor underlying cadiovasular disease.ObjectiveTo study the effects of uric acid on endothelial functions and to provide theoretical evidence to treat hyperuricemiaMethods1) HUVECs were treated with uric acid of different concentrations (0、5、20mg/dl) for various durations(12h,24h,48h,72h). Real-time PCR and Western Blotting were used to evaluate eNOS and ICAM-1gene and protein expression. ELISA was used to test the sICAM-1of supernate.2) HUVECs were treated with uric acid for24h and then the culture media was changed for lower uric acid for48h. Western Blotting and ELISA were used to evaluate the ICAM-1of cellular membrane and supernate respectively.Results1) Compared with control, with the presence of20mg/dl uric acid, eNOS mRNA was down-regulated at12h (P<0.05) and up-regulated at24h and48h(P<0.05) and no obvious difference was observed at72h, on the other hand, eNOS protein expression was down-regulated at72h and no obvious difference was observed at12-48h. With the stimulation of20mg/dl uric acid, HUVECs highly expressed ICAM-1mRNA at24-72h (P<0.05) and lowly expressed membrane ICAM-1protein compared with control group. sICAM-1was increased after24h in20mg/dl uric acid group.2) In the group with20mg/dl uric acid changed to Omg/dl, membrane ICAM-1and sIC AM-1protein expressions were up-regulated, though not significantly, compared with any control group without changing uric acid concentration.ConclusionHigh level uric acid can cause endothelial dysfunction by down-regulating eNOS protein expression, up-regulating ICAM-1mRNA expression and sICAM-1protein expression. Normal level uric acid can protect endothelial cells by down-regulating ICAM-1, which makes normal level uric acid meaningful to human beings. Changing uric acid concentration makes no benefits to the endothelium which suggests sudden concentration change might be a kind of injury to the endothelial cells.