Fig. 7.

HDAC inhibition blocks platelet aggregation in solution. A: washed human platelets (2 × 10⁸/ml) were incubated with vehicle (DMSO) or the HDAC6-specific inhibitor tubacin (10 μM) prior to stimulation with increasing concentrations of CRP, and the change in optical density indicative of platelet aggregation was recorded. Aggregation traces representative of three separate experiments are shown. B and C: washed human platelets (2 × 10⁸/ml) were incubated with vehicle (DMSO) or the pan-HDAC inhibitor TSA (10 μM) (B) or the SIRT1 inhibitor EX 527 (10 μM) or the SIRT2 inhibitor AGK2 (10 μM) (C) prior to stimulation with CRP (10 μg/ml) in the presence of 2 U/ml apyrase, and the change in optical density indicative of platelet aggregation was recorded. D and E: platelet surface P-selectin levels (D) and integrin αIIbβ3 activation (PAC-1) (E) analyzed by flow cytometry following vehicle (DMSO), TSA, and tubacin treatment and incubation with vehicle (white bars) or CRP (1 μg/ml; black bars) stimulation. MFI, mean fluorescence intensity. Data are represented as means ± SE.