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Cardiovascular disease due to atherosclerosis is the leading cause of death worldwide. Platelets have a fundamental role in atherothrombosis, but their role in atherogenesis is unclear. Herein, the purpose of this study was to determine anti-platelet drug ticagrelor on function of the aortas in apolipoprotein E-deficient mice.
Apolipoprotein E-deficient mices were made atherosclerosis by feeding a high cholesterol diet, and simultaneously treated with ticagrelor (10 mg/kg ig.q24h) or vehicle from 0 day to 8 week. Blood samples were collected and serum levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were measured at 0 day, 1,4, and 8 week. Western blot was used to exam the expression of P2Y1 and P2Y12 protein of aortas of mice,histopathological changes of aortas were detected at 8 Week. Endothelium-dependent relaxation induced by 2-MeS-ADP (selective P2Y1/12 -receptor agonist) was examined in aorta rings of mice at 8 week.
Ticagrelor and vehicle did not decreased serum levels of TC, TG, HDL-C, LDL-C in the apolipoprotein E-deficient mices. Endothelium-dependent relaxations induced by 2-MeS-ADP were decreased in aortas of vehicle-treament apolipoprotein E-deficient mices comparing to vehicle-treament wild mices. In the same time, indomethacin and L-NAME augmented 2-MeS-ADP induced contraction in vehicle-treament apolipoprotein E-deficient mices comparing to vehicle-treament wild mices. Ticagrelor treament did not normalize relaxation or contractile responses induced by L-NAME, indomethacin and 2-MeS-ADP in aortas of apolipoprotein E-deficient mices. P2Y13 receptor expression was significantly reduced but P2Y1 and P2Y12 protein expression was increased in aortas of apolipoprotein E-deficient mices. Endothelium-dependent relaxation by acetylcholine-stimulation was reduced in vehicle-treament apolipoprotein E-deficient mices, and ticagrelor could improve endothelial function of aortas of apolipoprotein E-deficient mices.
Our data suggested that ticagrelor ameliorates aortic endothelium function of apolipoprotein E-deficient mices, but that mechanism was not clear.