Skip to main content
. 2015 May 27;27(1):189–201. doi: 10.1681/ASN.2014121241

Figure 5.

Figure 5.

A novel AHR antagonist suppresses thrombosis in a postendovascular interventional thrombosis model. (A) Flow loop model design. The flow loop system consists of silastic loops with a reactive segment lined by vSMCs loaded on rotor stages driven by motors and motion controllers. The entire rotor system is held within an incubator at 37°C and driven by motors connected remotely to the controllers, circuitry, and flow recorders. The wall motion creates bidirectional flows that are measured via onboard, extracorporeal flow probes built into the rotor stages. (Insert) Arial view of a loop, which fits onto the rotor stage and is placed in axial alignment. (B) Thrombogenicity of IS is significantly abrogated by AHR antagonist CB7993113. vSMCs grown on fibronectin-coated tubes were exposed to 25 μg/ml IS with or without 20 μM CB7993113 for 24 hours. The tubes were then loaded with blood in the flow loop system. Three representative flow loop tubes showing inhibition of clot formation are shown. (C) Hb and LDH values of the thrombi from flow loop tubes treated with IS with or without AHR antagonist are shown. An average of six independent tubes is shown. P=0.002 for Hb and P=0.02 for LDH of uremic serum compared with the control serum. Error bars=SEM. (D) An AHR antagonist significantly abrogates thrombogenicity of uremic sera. vSMCs grown on fibronectin-coated tubes were exposed to pooled 5% uremic serum with or without 20 μM CB7993113 for 24 hours. The tubes were then subjected to shear forces in the flow loop system with blood flowing on the surface. Three representative flow loop tubes for visual examination of the clot are shown. (E) Hb and LDH values of the thrombi from the flow loop tubes treated with uremic serum with or without an AHR antagonist are shown. The data are averaged from six tubes. P=0.02 for Hb and P<0.01 for LDH of uremic serum compared with the control serum. Error bars=SEM. (F) AHR antagonist efficacy in reducing TF correlates with IS levels. vSMCs were treated with sera from eight individual ESRD patients (marked with superscript “a” in Table 1) with 10 μM of CH223191. Percent reduction in TF expression in CH223191-treated cells was compared with vehicle-treated cells. Average TF reduction from two independent experiments was correlated with IS levels.