Ibrutinib inhibits plaque-induced, but not collagen-induced, platelet aggregate formation under arterial flow at shear rates of 600/s and 1500/s. Blood samples were incubated with DiOC6 for platelet labeling and with solvent control or ibrutinib for 15 minutes. (A) Perfusion at 600/s (calculated shear stress 19 dyn/cm2). Representative micrographs show the effect of DMSO (0.1%) or ibrutinib (1 µM) on platelet deposition onto plaque homogenate, plaque tissue sections, and collagen at 0 and 5 minutes after the start of blood flow (left panels). They also show the formation of platelet aggregates in controls and their inhibition by ibrutinib. Effect of ibrutinib on the kinetics of plaque- and collagen-induced platelet deposition (right panels). Residual plaque-induced platelet deposition with 1 µM ibrutinib is shown at an enlarged scale. (B) Perfusion at 1500/s (calculated shear stress 48 dyn/cm2). Representative micrographs show the effect of DMSO (0.1%) or ibrutinib (0.5 µM) on platelet deposition onto plaque homogenate and collagen at 0 and 5 minutes after the start of blood flow (left panels). Effects of ibrutinib (0.2 and 0.5 µM) on the kinetics of plaque- and collagen-induced platelet deposition (right panels). Data are mean ± SD (n = 5). Statistical significance at 5 minutes after the start of blood flow is indicated. Scale bars = 100 μm. *P < .05, **P < .01, ***P < .001.
