18 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 ¹⁸ F-fluorodeoxyglucose ( ¹⁸ 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. ¹⁸ 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.  ¹⁸ 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, ¹⁸ F-FDG PET-MR imaging failed to demonstrate in vivo increased aortic glucose uptake in these models.
Competing Interests: Declarations Ethical approval All animal procedures were approved by the regional animal ethics committee (Comité d’Éthique NOrmand en Matière d’EXpérimentation Animale, CENOMEXA 054, n°29982) and were performed in accordance with the European directive 2010/63/EU on the protection of animals used for scientific purposes and specific French laws (decree n°2013–118). Competing interests The authors declare no competing interests.
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