Figure 1.
Ticagrelor but not clopidogrel increases endothelial healing and prevents neoatherosclerosis. (A) Protocol used to compare the effects of ticagrelor and clopidogrel effect on endothelial healing after vascular injury. The endovascular injury was performed in carotid arteries of wild-type (WT) mice, followed by administration of water (control), oral ticagrelor (20 mg/kg), or clopidogrel (16 mg/kg or 40 mg/kg) twice a day for 5 days. Carotid artery endothelial healing was then analyzed by en face staining. (B) Ticagrelor plasmatic concentration in mice 2 hours and 8 hours after administration. (C-E) Representative confocal images (C) and quantification of deendothelialized area of en face carotid arteries (E) stained with Evans blue or anti–VE-cadherin from the indicated treatments. Scale bar: 0.5 mm. The zone outlined in white represents the initial deendothelialized area, and the zone outlined in yellow represents the area that has not been recovered with endothelial cells. (F) Platelet aggregation of WT mice treated with ticagrelor and clopidogrel following ADP stimulation (10 μM). (G) Quantification of tail bleeding time of mice treated with vehicle (control), ticagrelor (n = 4), or clopidogrel (n = 4). (H) Protocol used to investigate ticagrelor impact on atherosclerosis development after vascular injury in vivo. Seven-week-old LDLR–/– mice were fed a 1.25% cholesterol diet for 35 days. Endovascular injury was performed in carotid arteries on day 14 and then treated by oral administration of ticagrelor (20 mg/kg) or clopidogrel (16 mg/kg) twice a day for 5 days (upper panel). Atherosclerotic plaque development was then analyzed by immunohistochemistry on day 35 as schematized in the lower panel. (I) Atherosclerotic lesions were measured on histological sections located 0, 50, and 100 μm from the carotid bifurcation as schematized in panel H. (J) Representative confocal images of atherosclerosis stained with Nile red (yellow) and DAPI (blue) (scale bar: 50 μm). Data are expressed as means ± standard error of the mean (SEM) and compared using an analysis of variance (ANOVA) test followed by Bonferroni’s post hoc test. Values of P <.05 were considered statistically significant.

Ticagrelor but not clopidogrel increases endothelial healing and prevents neoatherosclerosis. (A) Protocol used to compare the effects of ticagrelor and clopidogrel effect on endothelial healing after vascular injury. The endovascular injury was performed in carotid arteries of wild-type (WT) mice, followed by administration of water (control), oral ticagrelor (20 mg/kg), or clopidogrel (16 mg/kg or 40 mg/kg) twice a day for 5 days. Carotid artery endothelial healing was then analyzed by en face staining. (B) Ticagrelor plasmatic concentration in mice 2 hours and 8 hours after administration. (C-E) Representative confocal images (C) and quantification of deendothelialized area of en face carotid arteries (E) stained with Evans blue or anti–VE-cadherin from the indicated treatments. Scale bar: 0.5 mm. The zone outlined in white represents the initial deendothelialized area, and the zone outlined in yellow represents the area that has not been recovered with endothelial cells. (F) Platelet aggregation of WT mice treated with ticagrelor and clopidogrel following ADP stimulation (10 μM). (G) Quantification of tail bleeding time of mice treated with vehicle (control), ticagrelor (n = 4), or clopidogrel (n = 4). (H) Protocol used to investigate ticagrelor impact on atherosclerosis development after vascular injury in vivo. Seven-week-old LDLR–/– mice were fed a 1.25% cholesterol diet for 35 days. Endovascular injury was performed in carotid arteries on day 14 and then treated by oral administration of ticagrelor (20 mg/kg) or clopidogrel (16 mg/kg) twice a day for 5 days (upper panel). Atherosclerotic plaque development was then analyzed by immunohistochemistry on day 35 as schematized in the lower panel. (I) Atherosclerotic lesions were measured on histological sections located 0, 50, and 100 μm from the carotid bifurcation as schematized in panel H. (J) Representative confocal images of atherosclerosis stained with Nile red (yellow) and DAPI (blue) (scale bar: 50 μm). Data are expressed as means ± standard error of the mean (SEM) and compared using an analysis of variance (ANOVA) test followed by Bonferroni’s post hoc test. Values of P <.05 were considered statistically significant.

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