Abstract

BACKGROUND: Ticagrelor is the first oral anti-platelet agent which has direct anti-platelet aggregation effect by combining with ADP P2Y12 receptors in platelets. It has been approved to reduce the incidence of thrombus cardiovascular events in acute coronary syndrome patients. However, the effects of ticagrelor on endothelial apoptosis have not been investigated.

MATERIAL AND METHODS: Oxidized low-density lipoprotein (ox-LDL) was used to establish a human umbilical vein endothelial cell (HUVEC) apoptosis model. To investigate the effects of ticagrelor on endothelial apoptosis, the HUVECs were treated with different dose of ticagrelor. Apoptosis rates of HUVECs was evaluated by flow cytometry, and the expression levels of Akt, p-Akt, Bcl-2, Bax, caspase-3, endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) concentration were assessed.

RESULTS: After treatment with 50 ug/mL ox-LDL or 100 ug/mL ox-LDL, we found that the late apoptosis and necrosis rate and the expression levels of Bax and caspase-3 were significantly increased in HUVECs, whereas the expression levels of Akt, p-Akt, Bcl-2, eNOS, and NO were significantly decreased. Ticagrelor restored the apoptosis rate of ox-LDL-induced HUVECs in a dose-dependent manner. In addition, compared with ox-LDL group, ticagrelor treatment significantly increased the expression levels of Akt, p-Akt, Bcl-2, eNOS, and NO concentration, and significantly decreased the expression levels of Bax and caspase-3.

CONCLUSIONS: We found that ox-LDL induced significant apoptosis and necrosis in our model, which was dose-dependently improved by ticagrelor. These changes might be explained by alterations in apoptosis and antioxidant pathways.

Keywords: Apoptosis Inducing Factor, Platelet Aggregation Inhibitors, Proto-Oncogene Proteins c-akt, Receptors, Oxidized LDL, Cells, Cultured, Human Umbilical Vein Endothelial Cells, Lipoproteins, LDL, Necrosis, Nitric Oxide, Nitric Oxide Synthase Type III, Proto-Oncogene Proteins c-bcl-2, ticagrelor, bcl-2-Associated X Protein