AIM:To investigate the effect of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) on the Notch signaling pathway in a model of oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) damage.METHODS:HUVECs were divided into control group, ox-LDL group, DAPT group and ox-LDL+DAPT group.The morphological changes of the HUVECs with different treatments were observed under light microscope.The viability of the HUVECs was measured by CCK-8 assay.The protein expression levels of Notch1, Notch4 and Jagged1 were determined by Western blot.RESULTS:ox-LDL induced great damage to the HUVECs, evidenced by increased cell death and debris in the culture.However, the cell damage was abolished by adding DAPT into the culture.The viability of the HUVECs was increased by co-treatment with DAPT and ox-LDL.ox-LDL treatment significantly decreased the protein expression levels of Notch1 and Jagged1, and elevated Notch4.However, these changes were totally reversed by DAPT.None of these proteins showed significant change in the HUVECs co-treated with DAPT and ox-LDL as compared with control group.CONCLUSION:ox-LDL is able to induce HUVEC damage in vitro.DAPT attenuates ox-LDL-induced damage in the HUVECs by regulating the Notch signaling pathway.