1. Fig. 1. IS mediates a hyperthrombotic uremic phenotype in an AHR-dependent manner across CKD stages.
IS mediates a hyperthrombotic uremic phenotype in an AHR-dependent manner across CKD stages. (A) Mean blood concentrations of IS in 10- to 14-week-old male and female C57BL/6 mice (n = 5 per time point) are shown. The P values correspond to an increase in IS concentrations compared to the probenecid group. No differences in blood concentrations of IS were noted between male and female mice. The dashed line represents the average concentration of IS in ESRD patients (11, 47). Student’s t test was performed. Data are shown as means ± SD. (B) Representative traces of carotid artery flow in C57BL/6 animals before and 20 min after the application of 10% FeCl3 (n = 8 per group). The time for the blood flow to drop below ml/min was considered as TtO (arrow). (C) Representative images from hematoxylin and eosin–stained carotid arteries collected after the FeCl3 procedure. Representative images from six vessels per group are shown. Scale bars, 25 μm. RT, right; LT, left. (D) Mean TtO (n = 8 per group) after 5 days of exposure to IS and IS + CH Student’s t test was performed. Data are shown as means ± SD. (E) Mice were exposed to probenecid + IS for 5 days and then subjected to the FeCl3 thrombosis assay. Thirty minutes before the assay, control antibody or rat anti-mouse TF neutralizing antibody was administered. Mean TtO (n = 6 per group) is shown. Data are shown as means ± SEM. (F) Mean TtO in the photochemical thrombosis model in probenecid and probenecid + IS mice (n = 6 per group). Student’s t test was performed. Data are shown as means ± SEM. (G) Relationship between TtO and different concentrations of IS in 16 animals. IS concentrations from different stages of human CKD are shown (3, 11). A Pearson correlation analysis was performed.
Moshe Shashar et al., Sci Transl Med 2017;9:eaam8475
Published by AAAS