Extended Data Fig. 8: Role of IDO1 in pressure-overload related cardiac pathophysiology and experimental atherosclerosis.

a, Cardiac expression of Ido1 mRNA after sham and TAC for 21 days (n = 3 mice per treatment), with IFN-γ-treated hearts (n = 2 mice) as positive control. Inset, increase in ventricle weight-to-tibia length ratio as evidence for TAC-induced cardiac hypertrophy. b, c, IDO1 staining (brown colour) of (b) atherosclerotic lesions in thoracic aorta and (c) resistance vessel in kidney of Apoe^−/− (top, representative of n = 1 and 4 mice for b and c, respectively) and Apoe^−/−Ido1^−/− mice (bottom, representative of n = 2 and 3 mice for b and c, respectively) after six months of Western diet. Middle panels represent rabbit negative immunoglobulin fraction control staining of (b) atherosclerotic lesions in thoracic aorta (representative of n = 1 mouse) and (c) resistance vessels in kidney (representative of n = 4 animals) of Apoe^−/− mice after six months of Western diet. For each animal, sections were taken in duplicate. Magnification 60× (b) and 20× (c). Arrow heads (c) indicate microvessels. d, Plasma concentrations of Trp and Kyn in Apoe^−/− and Apoe^−/−Ido1^−/− mice after six months of Western diet with n indicating the number of animals used. e, Trp-induced relaxation of pre-constricted, atherosclerotic lesion-containing aortic rings isolated from Apoe^−/− and Apoe^−/−Ido1^−/− mice in the presence or absence of IDO1 inhibitor 1-MT after six months of Western diet with individual data points reflecting the number of animals used for each treatment. f, Systolic blood pressure (SBP) of Apoe^−/− and Apoe^−/−Ido1^−/− mice before (−) and after (+) administration of 1-D-MT (n = 6 animals for each group). The specific P values indicated were derived from a two-tailed Mann Whitney (d) and Kruskal–Wallis test with Dunn’s multiple comparisons (e, f).