Figure 4
PXR ligands function in a species-specific manner and inhibit thrombus formation in vitro. Human or mouse PRP was treated with (A) SR12813 or (B) PCN or vehicle-control (0.1% DMSO v/v for SR12813 or 0.5% v/v DMSO for PCN) prior to stimulation with CRP-XL (0.25 µg/ml for human platelets and 0.5 µg/ml for mouse platelets). The level of fibrinogen binding to integrin αIIbβ3 was measured using flow cytometry. Human or mouse blood, incubated with DiOC6 (5 μM) were perfused through collagen-coated (100 μg/ml) microfluidic chips at arterial flow rate (20 dyne/cm2) after treatment with (C,D) SR12813 or (E,F) PCN or vehicle-control (0.1% DMSO v/v for SR12813 or 0.5% v/v DMSO for PCN) for 20 minutes. Representative images display thrombus formation. Quantified data represent mean thrombus fluorescence intensity normalised to fluorescence level of the vehicle-treated sample obtained at the end of the assay. Data represent mean ± SD (n ≥ 3) where *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001 was determined by student t-test or one-way ANOVA for fibrinogen binding assay and two-way ANOVA for in vitro thrombus formation assay. Figure adapted from corresponding PhD thesis48.
