Treatment with linagliptin attenuates thrombin-induced platelet aggregation in vitro. Representative aggregometry traces of mouse platelets incubated for 10 min with linagliptin (10–100 μM) and stimulated to aggregate with 0.05 U/ml (A,B) or 0.1 U/ml (C,D) of thrombin. (B,D): Error bars represent the SEM. n = 4–7/group. *p < 0.05 vs. vehicle and linagliptin (10 μM); **p < 0.05 vs. vehicle. E–H: Representative aggregometry traces of mouse platelets incubated for 10 min with linagliptin (10–100 μM) and stimulated to aggregate with 5 μg/ml collagen (E,F) and 10 μM ADP (H,I). *p < 0.05 vs. vehicle and linagliptin (10 μM); (I,J): Effects of Lina on mice platelet adhesion. (I) Representative of images of platelet adhesion after Lina treatment, platelets were pre-labeled with CMFDA, scale bar = 20 μm. (J) Quantification of the relative adhesion by pixel density measurements in platelets. All data were expressed as the means ± SEM. Statistical comparisons were performed using the two-way ANOVA. *p < 0.05 vs. vehicle and linagliptin (10 μM). (K,L): Platelets were prepared for transmission electron microscopy imaging, and images were acquired using a Tecnai-12 electron microscope at ×4,300 magnification. (K) The distribution of granules (L) (scale bar: 1 μm) and mitochondria (F) (dark arrow) (scale bar: 500 nm) throughout the platelet. Images are representative of three independent observations. Resting: a,b,e,f; Thrombin: c,d,g,h.