F-fluorodeoxyglucose PET-MR characterization of aortic inflammation in ApoE mouse models of accelerated atherosclerosis: comparison of Western diet vs. uremia.

ApoE mice are a widely used preclinical model of atherosclerosis, potentially accelerated by a Western diet (WD) or uremia. We aimed to compare hybrid F-fluorodeoxyglucose (F-FDG) positron emission tomography-magnetic resonance (PET-MR) and immunostaining in ApoE models of accelerated atherosclerosis. Five groups were studied: standard diet-fed ApoE (n = 7), standard diet-fed and uremic ApoE (n = 7), WD ApoE (n = 7), WD and uremic ApoE (n = 6), and control C57BL/6J mice (n = 6). Uremia was induced by electrocoagulation of the right kidney at 8 weeks old, followed 2 weeks later by a contralateral nephrectomy. F-FDG PET-MR imaging and histological staining (anti-CD4, -CD8, -CD11c, -CD20, -CD31, -CD68, -CD163, -interferon-γ, interleukin-1α, -1β, -6, -17 A antibodies) were performed in 18-week-old mice, i.e., 8 weeks after 5/6 nephrectomy and/or WD. F-FDG uptake was similar in all groups. In contrast, histological staining highlighted higher percentages of CD8-, CD68-, or CD11c-positive cells in ApoE aortic samples than in wild-type aortic samples. In addition, immunostaining revealed some differences between ApoE mouse groups. Only the WD seemed to contribute to these differences. Using immunostaining, WD appeared to be a stronger accelerator of atherosclerosis than uremia. However, F-FDG PET-MR imaging failed to demonstrate in vivo increased aortic glucose uptake in these models.