Fig. 8.
CCR5 inhibition results in loss of enhanced recruitment of patrolling monocytes, Mafb+AIM+ macrophage accumulation and AT acceleration in MT4-MMP-null BMT Ldlr–/– mice. a Scheme depicts the experimental design of CCR5 blocking strategy by Maraviroc (MRV) administration as described in M&M. b Representative orthogonal XZ view of confocal microscopy images of whole mount-stained aortic arch from Ldlr–/– mice transplanted with MT4-MMP+/+ or MT4-MMP–/– BM cells, fed the HFD for 3 days and treated with MRV or vehicle. Samples were stained for CD115 (red) and Ly6C (green); elastin autofluorescence (green) and nuclei (Hoechst, blue) are also shown. Scale bar, 20 µm. The bar graph (right) shows the quantification of the number of patrolling monocytes (CD115+Ly6C–) in the aorta lumen; n = 7 vehicle and n = 8 MRV mice per genotype in two independent experiments. c Bar graphs show the quantification of the number of Mac3+ cells (left), Mac3+Mafb+ cells (middle), and Mac3+Mafb+AIM+ cells (right) in the plaques of BM-transplanted Ldlr–/– mice fed a HFD for 1 week and treated with Maraviroc or vehicle. n = 8 mice per genotype and condition in two independent experiments. d Representative microscopy images of transverse sections of aortic sinus from BM-transplanted Ldlr–/– mice fed a HFD for 8 weeks and treated with Maraviroc or vehicle; sections were labeled for Mac3 (red) and Hoechst (blue; nuclei) (upper, scale bar, 50 µm) and graph shows the quantification of the number of Mac3+ cells in the plaque (lower). n = 7 vehicle and n = 8 MRV BM-transplanted mice per genotype in two independent experiments. e Graph showing the lesion area of aortas stained with Oil Red from BM-transplanted Ldlr–/– mice fed a HFD for 8 week and treated with MRV or vehicle. n = 7 and n = 8 mice for Vehicle and MRV mice per genotype in two independent experiments. f Stary scoring (I-VI) of transverse aortic H&E-stained sections from BM-transplanted Ldlr–/– mice fed a HFD for 8 weeks and treated with Maraviroc or vehicle, shown as a percentage of all mice for each score. n = 7 vehicle and n = 8 MRV BM-transplanted mice per genotype in two independent experiments. Data were tested by one-way ANOVA followed by Bonferroni’s post test in b–e and by χ2-test for a trend in f. Results are expressed as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.005