Fig. 4: Blockade of I1R prevents atherosclerosis induction by ImP or high-cholesterol diet.
From: Imidazole propionate is a driver and therapeutic target in atherosclerosis
a, Ldlr−/− mice grafted with bone marrow from control Nischfl/fl (Ctrl, n = 17; ImP, n = 20) or Lyz2ΔNisch (Ctrl, n = 19; ImP, n = 18) and fed chow diet for 12 weeks. Oil red O staining of aortic arch (left) and representative images of aorta (right). b–g, Chow-fed Apoe−/− mice were treated as indicated. b, Oil red O staining of aortic arch (left) and representative images of aorta (right). Ctrl, n = 15; ImP, n = 17; ImP + AGN, n = 16. c, Left, Ly6Chi monocytes in blood at endpoint (n = 15). Right, representative density plots. d, IFNγ and TNF in plasma. n = 10. e, Left, p-S6 staining in peritoneal macrophages. Ctrl, n = 10; ImP, n = 9; ImP + AGN, n = 10. Right, representative histograms. f, Ratio of TH1 to Treg cells infiltrated in aorta. Ctrl, n = 9; ImP, n = 7, ImP + AGN, n = 7. g, F4/80+CD86+ cells infiltrated in aorta. n = 10. f,g, Left, individual data. Right, representative density plots. h–m, Apoe−/− mice were fed a chow diet or HC diet for 8 weeks; AGN192403 was added to the HC group (HC + AGN) in the last 4 weeks. h, Oil red O staining of aortic arch (left) and representative images of aorta (right). Chow, n = 15; HC, n = 14; HC + AGN, n = 13. i, Masson’s trichrome staining of aortic roots. Quantification of lesions in aortic roots (left), necrotic core area (middle) and representative images (right). Arrowheads indicate necrotic areas. Chow, n = 12; HC, n = 13; HC + AGN, n = 14. Scale bars, 500 µm. j,k, Individual data (left) and representative density plots (right) for flow cytometry quantification of blood Ly6Chi monocytes (j; chow, n = 12; HC, n = 13; HC + AGN, n = 13) and T-bet+ CD4+ TH1 cells (k; chow, n = 10; HC, n = 9; HC + AGN, n = 10). l, Plasma IFNγ and TNF. Chow, n = 10; HC, n = 9; HC + AGN, n = 10. m, Individual data (left; chow, n = 12; HC, n = 10; HC + AGN, n = 11) and representative histograms (right) for p-S6 staining in peritoneal macrophages. a–m, Individual data points and mean ± s.e.m. from at least two pooled independent experiments. One-way ANOVA with Tukey post hoc correction.
