Figure 7. Expression of a Constitutively Active AHR Decreases Capillary Density and alters Angiogenic Signaling in Male Mice with Normal Kidney Function.

(A) Schematic of the experimental design. (B) Generation of a mutant constitutively active AHR (CAAHR). (C) Quantification of mRNA levels of Ahr and Cyp1a1 in mice (n=4/group/sex). (D) Perfusion recovery in the gastrocnemius muscle (n=10/group/sex). (E) Representative images of the tibialis anterior muscle labeled for endothelial cells and quantification of capillary density (n=10 AAV-HSA-GFP/sex, 6 male and 9 female AAV-HSA-AHR, and 7 AAV-HSA-CAAHR/sex). (F) Representative images of the tibialis anterior muscle labeled for pericytes and quantification of pericyte density (n=10 male and 8 female AAV-HSA-GFP, 10 male and 9 female AAV-HSA-AHR, and 10 AAV-HSA-CAAHR/sex). (G) Representative images of the tibialis anterior muscle labeled for arterioles and quantification of arteriole density (n=9 male and 8 female AAV-HSA-GFP, 9male and 10 female AAV-HSA-AHR, and 10 AAV-HSA-CAAHR/sex). (H) Vascular-associated gene expression in AAV-HSA-GFP and AAV-HSA-CAAHR muscle via bulk RNA sequencing analysis (n=3 males/group). Analysis of panels C-G was performed using two-way ANOVA with Sidak’s post hoc testing for multiple comparisons. Analysis in Panel H involved false-discovery rate corrected Wilcoxon test. Error bars represent the standard deviation.