Hcy Induces Endothelial Injury By Regulating The DNA Methylation Status Of P66Shc

BackgroundEpidemiological and clinical studies have shown that hyperhomocysteinemia(HHcy)is an independent risk factor for cardiovascular disease.In the mechanism of HHcy induced cardiovascular disease,Hcy induced vascular endothelial cell injury is one of the important factors.The results showed that the methylation of P66 Shc could cause vascular endothelial cell damage.Whether Hcy can change the methylation state of P66 Shc and cause vascular endothelial cell damage is rarely reported.In this study,human umbilical vein endothelial cells(HUVECs)were cultured in vitro to observe the effect of Hcy on the DNA methylation of P66 Shc cells and the effect of DNA methylation on the apoptosis of HUVECs.ObjectiveTo investigate whether homocysteine(Hcy)can cause endothelial damage by reducing the DNA methylation of P66 Shc.Methods 1.Human umbilical vein endothelial cells were cultured and Hcy was added to induce the injury of human umbilical vein endothelial cells;2.DNA methylation of P66 Shc was detected by methylation specific PCR;3.The expression of P66 Shc and active-Caspase-3 was detected by adding 5-Azacytidine,a methylation inhibitor of different concentrations.Results 1.Hcy increased the expression of P66 Shc and active-Caspase-3 in HUVECs;2.Hcy induced DNA hypomethylation of P66Shc;3.The expression of P66 Shc and active-Caspase-3 protein can be down regulated by adding 5-Azacytidine.ConclusionsHcy can reduce the DNA methylation of P66 Shc and induce apoptosis of endothelial cells,which leads to endothelial damage.