Figure 2.
Ticagrelor-induced endothelial healing is dependent on adenosine and A2A receptor activation. (A) Quantification of deendothelialized area (upper panel) and representative confocal images of en face carotid arteries (lower panel) cultured ex vivo in control media, or in media containing ticagrelor (10 μM), or P2Y12 inhibitor AR-C69931MX (10 μM) and stained with anti–VE-cadherin. (B) Quantification of deendothelialized area (upper panel) and representative confocal images of en face carotid arteries (lower panel) cultured ex vivo in control media or in media containing ticagrelor (10 μM) or dipyridamole (10 μM) and stained with anti–VE-cadherin. (C) Quantification of deendothelialized area (upper panel) and representative confocal images of en face carotid arteries (lower panel) cultured ex vivo in control media or in media containing ticagrelor (10 μM) with or without KW6002 (1 μM) and stained with anti–VE-cadherin. (D) Quantification of deendothelialized area (upper panel) and representative confocal images of en face carotid arteries cultured ex vivo in control media or in media containing a nonselective adenosine receptor agonist, NECA, or an A2A receptor–specific agonist, CGS21680, and stained with anti–VE-cadherin. The zone outlined in yellow represents the area that has not been recovered with endothelial cells. Scale bar: 0.5 mm. (E) Bright-field microscopy images of scratch wound healing assay in arterial endothelial cells treated with vehicle or CGS21680 (1 mM) at the indicated times. The scratch edge is demarcated by the white dotted line (n = 6). Scale bar = 200 μm. (F) Quantification of migration speed of scratch wound healing assay in the indicated conditions. Data shown are means ± SEM. ∗P < .05. The statistical significance of differences between 2 groups was determined using the unpaired Student t test, and differences among multiple groups were determined using 1-way ANOVA followed by the Bonferroni post hoc test (intragroup comparisons). Values of P <.05 were considered statistically significant. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001.

Ticagrelor-induced endothelial healing is dependent on adenosine and A2A receptor activation. (A) Quantification of deendothelialized area (upper panel) and representative confocal images of en face carotid arteries (lower panel) cultured ex vivo in control media, or in media containing ticagrelor (10 μM), or P2Y12 inhibitor AR-C69931MX (10 μM) and stained with anti–VE-cadherin. (B) Quantification of deendothelialized area (upper panel) and representative confocal images of en face carotid arteries (lower panel) cultured ex vivo in control media or in media containing ticagrelor (10 μM) or dipyridamole (10 μM) and stained with anti–VE-cadherin. (C) Quantification of deendothelialized area (upper panel) and representative confocal images of en face carotid arteries (lower panel) cultured ex vivo in control media or in media containing ticagrelor (10 μM) with or without KW6002 (1 μM) and stained with anti–VE-cadherin. (D) Quantification of deendothelialized area (upper panel) and representative confocal images of en face carotid arteries cultured ex vivo in control media or in media containing a nonselective adenosine receptor agonist, NECA, or an A2A receptor–specific agonist, CGS21680, and stained with anti–VE-cadherin. The zone outlined in yellow represents the area that has not been recovered with endothelial cells. Scale bar: 0.5 mm. (E) Bright-field microscopy images of scratch wound healing assay in arterial endothelial cells treated with vehicle or CGS21680 (1 mM) at the indicated times. The scratch edge is demarcated by the white dotted line (n = 6). Scale bar = 200 μm. (F) Quantification of migration speed of scratch wound healing assay in the indicated conditions. Data shown are means ± SEM. ∗P < .05. The statistical significance of differences between 2 groups was determined using the unpaired Student t test, and differences among multiple groups were determined using 1-way ANOVA followed by the Bonferroni post hoc test (intragroup comparisons). Values of P <.05 were considered statistically significant. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001.

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