Trichostatin A Has Protective Effects On Endothelial Cells Injured By Hyperuricemia

BackgroundUric acid(UA)accumulation triggers endothelial dysfunction,oxidative stress and inflammation.Histone deacetylase(HDAC)play a vital role in regulating the pathological processes of various diseases.However,the influence of HDAC inhibitor on UA-induced vascular endothelial cell injury(VECI)remains undefined.Hence,this study aimed to investigate the effect of HDACs inhibition on UA-induced vascular endothelial cell dysfunction and its detailed mechanism.of blood vessels,and their dysfunction leads to the development of cardiovascular disease.Therefore,the protection of vascular endothelial cells is essential for the treatment of cardiovascular disease.AimsIn this study,We can study the damage caused by uric acid to vascular endothelial cells through in vivo and in vitro experiments,and whether TSA can reduce its damage.In other words,TSA may be one of the drugs to treat vascular endothelial cell damage caused by uric acid.MethodsUA was employed to induce human umbilical vein endothelial cell(HUVEC)injury.Meanwhile,potassium oxonate-and hypoxanthine-induced hyperuricemia mouse models were also constructed.A broad-spectrum HDAC inhibitor trichostatin A(TSA)was given to HUVECs and mice to determine whether HDACs can affect UA-induced VECI The nitric oxide and reactive oxygen species levels were determined using the corresponding commercial assay kits,while the levels of protein expression were determined by Western blot analysis.Results1.Pretreatment of HUVECs with TSA attenuated UA-induced inflammation,oxidative stress and endothelial-interstitial transformation.2.Western blot analysis showed that TSA increased FGF21 expression and phosphorylation of AKT and e NOS.These effects could be reversed by FGF21 knockdown.3.Western blot analysis demonstrated that TSA could increase FGF21 expression and phosphorylation of AKT and e NOS in aortic and renal tissues.ConclusionHDACs alleviated UA-induced VECI through upregulating FGF21 expression and then activating PI3K/AKT pathway.