Figure 6.
Kyn-mediated venous thrombogenicity and TF and PAI-1 are suppressed by AHR inhibition. (A) Experimental design. A group of 12 mice (6 male mice and 6 female mice) were divided into 2 equal groups, with 3 male mice given 10 mg/kg CH2213191 or vehicle (used as control), and similarly, 3 female mice given 10 mg/kg CH2213191 or vehicle. The treatment was continued for 2 more days after IVC ligation. The clots from mice harvested after 48 hours following surgery were weighed. (B) IVC clot weights are presented as a box plot for each group. P = .112 compares control and CH223191-treated groups. (C) Scheme examining AHR inhibition in Kyn-mediated venous thrombosis. A group of 8- to 12-week-old athymic mice consisting of an equal proportion of male and female animals was injected IP with 100 mg/kg Kyn with or without 10 mg/kg CH223191, once daily before the procedure. Vehicle-treated mice served as a control group. The animals were subjected to the IVC ligation, and clots were harvested 48 hours after ligation. Control group, n = 6 mice; Kyn group, n = 8 mice; and Kyn + CH223191 group, n = 6 mice. (D) IVC clot weights presented as a box plot for each group from panel C. *P = .02 compares the control and Kyn groups, and **P = .03 compares the Kyn and Kyn + CH223191 groups. (E) TF and PAI-1 expression from each mouse was normalized to glyceraldehyde-3-phosphate dehydrogenase. Changes in the TF and PAI-1 expression (as measured by western blotting) compared with the controls (the dotted line) of mice from panel C are shown. The borders of the box depict 25th and 75th percentiles, and whiskers correspond to minimum and maximum values. The number of mice is listed in panel A. Student t tests were performed. Compared with the control mice, *P = .02, **P = .04. Compared with the Kyn-injected mice, #P = .03 and ##P = .01. No significant difference was noted in TF and PAI-1 between the control and Kyn + CH223191 groups.