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Atherosclerosis is now generally accepted as a chronic inflammatory condition. There is an association between cardiac inflammation and fibrosis with the presence of atherosclerosis. Therefore, the aims of the current study were to investigate any impact of P2Y12 receptor inhibitor ticagrelor inhibition cardiac inflammation and fibrosis 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 lipoproteincholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were measured at 0 day, 1,4, and 8 week. The structure and blood flow in heart of mice was observed by echocardiographic measurements, Real-time PCR was used to measure inflammatory cell infiltration responsible for cardiac fibrosis into the heart, CD41 staining showed mice platelets accumulation at heart at 8 week.
Ticagrelor and vehicle did not decreased serum levels of TC, TG, HDL-C, LDL-C in apolipoprotein E-deficient mice at 0 day, 1,4, and 8 week. CD41 staining showed that heart platelets accumulated in vehicle-treatment apolipoprotein E-deficient mices were more than wild mices. Ticagrelor- treatment apolipoprotein E-deficient mices had significantly decreased accumulation of cardiac fibrosis and α-SMA(+) myofibroblasts comparing to those in vehicle-treatment apolipoprotein E-deficient mices. Inflammatory cells: CD45(+)Ly6G(+) neutrophils and Mac-2(+) macrophages in heart of ticagrelor- treatment apolipoprotein E-deficient mices were also inhibited comparing to those of vehicle-treatment apolipoprotein E-deficient mices. Transforming growth factor-β and Interleukin-1β examed by immunohistochemical staining and Real-time PCR in heart were signifcantly decreased in ticagrelor-treatment apolipoprotein E-deficient mices comparing to those of vehicle-treatment apolipoprotein E-deficient mices.
Our data suggested that ticagrelor ameliorates cardiac inflammation and fibrosis in the heart of apolipoprotein E-deficient mice.