Effect of chronic peripheral CB1 antagonist administration on atherosclerosis and macrophage proliferation. (A) Experimental scheme. Ldlr^−/− mice were fed with Western diet (WD) for 8 weeks and subjected to daily iv injections of JD5037 (3 mg/kg) or vehicle for the last 4 weeks. (B) Representative images of aortic root cross-sections stained with ORO. (C) Representative images of HE-stained aortic arch longitudinal sections. (D) Quantification of absolute lesion area within aortic roots (n = 7–8 mice) or (E) normalized to IEL (n = 7–8). (F) Quantification of the plaque area in aortic arch sections (n = 7–8). (G) Representative images of proliferating (Ki67+, green; white arrowheads) macrophages (CD68+, red) in aortic root plaques; nuclei were counterstained with Hoechst (blue). Scale bar: 100 μm (left) and 10 µm (right). (H) Quantification of lesional macrophage area (n = 6) and (I) total as well as relative counts of proliferating plaque macrophages (n = 5–6). Each dot represents one biologically independent mouse sample and all data are expressed as mean ± S.E.M. Two-sided unpaired Student’s t-test (D–F, H, I). Male and female were analysed independently.