Effect And Mechanism Of Selenium Nanoparticles With Different Surface Charges And Sizes On Vascular Endothelial Cell Dysfunction

The incidence and mortality of cardiovascular disease(CVDs)are the first and are still on the rise.Atherosclerosis(AS)is the main pathological basis of CVD.It is of great significance to study the prevention and treatment of AS.Endothelial dysfunction is a key promoting factor in the formation and development of AS.It has reported that optimal selenium intake can prevent AS by inhibiting oxidative stress,inflammatory,vascular cell apoptosis and vascular calcification.Compared with traditional inorganic selenium,selenium nanoparticles(Se NPs)has drawn much attention in biomedicine due to its biological activity and lower toxicity.Our previous study has demonstrated that the supplement of Se NPs could significantly alleviate hyperlipidemia and oxidative stress in animal model of AS,implying a potential promise of Se NPs for the prevention of AS.As we all known,the interaction between nanomaterials and cells depends not only on the shape of nanoparticles,but also on the surface properties and size of nanomaterials.Therefore,in present study,human umbilical vein endothelial cells(EA.hy 926)were used as the research object to investigate the effects of different surface charge and size of Se NPs on vascular endothelial dysfunction,a key initiation factors of the formation and development of AS,and the potential mechanism,which may provide a mechanism explanation of Se NPs for preventing AS and provide experimental basis for designing nanometer medical materials.The main results are as follows:(1)The effect of different surface charge of Se NPs on endothelial cell dysfunction and its potential mechanismA chemical reduction was used to synthesize Se NPs with positive charge(CS-Se NPs)and negative charge(SA-Se NPs).The oxidative damage model of endothelial cells established in EA.hy 926 induced by H2O2 was used to investigate the effect of different surface charge of Se NPs on endothelial cell function and its potential mechanism.The results showed that the viability of endothelial cells and the expression of antioxidant selenoenzymes were increased,and the oxidative stress level and the expression levels of key genes associated the endothelial dysfunction was decreased after the pretreatment of CS-Se NPs and SA-Se NPs compared with the cells treated with H2O2 alone.These results suggest that CS-Se NPs and SA-Se NPs can regulate Keap1-Nrf2 /ARE signaling pathway reduce oxidative stress injury induced by H2O2 through activating selenoenzymes and selenoprotein,and thus inhibit endothelial cell injury and dysfunction.There was no significant difference between SA-Se NPs and CS-Se NPs on alleviating oxidative damage of vascular endothelial cells induced by H2O2.(2)The effect of different sizes of Se NPs on endothelial cell dysfunction and its potential mechanismDifferent sizes of Se NPs were synthesized by controlling the reaction conditions at the presence bovine serum albumin(BSA).The above oxidative injury model of endothelial cells were used to investigate the effect of different sizes of Se NPs on endothelial cell function and its potential mechanism.The results showed that the viability of endothelial cells and the expression of antioxidant selenoprotein and selenoenzymes were increased,and the oxidative stress level and the expression of key genes associated the endothelial dysfunction was inhibited after the pretreatment of different sizes of Se NPs compared with the cells treated with H2O2 alone,indicating that three sizes of Se NPs can alleviate the oxidative stress injury induced by H2O2 through activating selenoenzymes and selenoprotein,and thus inhibit endothelial cell injury and dysfunction.In general,the effect of Se NPs with large size on the alleviation of H2O2-induced oxidative damage in endothelial cells was superior to that of the other little sizes of Se NPs.