Effects of atorvastatin and diet interventions on atherosclerotic plaque inflammation and [18F]FDG uptake in Ldlr−/−Apob100/100 mice

Abstract Background and aims Uptake of the positron emission tomography (PET) tracer 2-deoxy-2-[ 18 F]-fluoro-d- glucose ([ 18 F]FDG) into macrophages is a sensitive marker of inflammation in atherosclerosis. To assess the anti-inflammatory effects of statins, we studied whether atorvastatin therapy reduces aortic [ 18 F]FDG uptake in hypercholesterolemic mice deficient in low-density lipoprotein receptor (Ldlr), and expressing only apolipoprotein B-100 ( Ldlr −/− Apob 100/100 ). Methods Thirty-six Ldlr −/− Apob 100/100 mice were fed a high-fat diet (HFD) for 12 weeks and then allocated to receive a HFD (n = 13), chow diet (Chow, n = 12), or HFD with added atorvastatin (HFD + A, n = 11), for another 12 weeks. In addition to aortic histopathology, [ 18 F]FDG uptake was studied in vivo using PET/computed tomography (CT), and ex vivo by gamma counting of excised aorta. Results Total cholesterol levels were lower in the Chow and HFD + A groups than in the HFD group (10 ± 3.2, 23 ± 4.9 and 34 ± 9.2 mmol/l, respectively), with the Chow group also showing a lower plaque burden and lower numbers of macrophages in the lesions. Compared to the HFD group, [ 18 F]FDG uptake in the aorta (normalized for blood) was lower in the Chow group in both in vivo (2.1 ± 0.21 vs . 1.7 ± 0.25, p  = 0.018) and ex vivo (5.2 ± 2.3 vs . 2.8 ± 0.87, p  = 0.011) analyses, whereas atorvastatin had no effect on uptake (2.1 ± 0.42 in vivo and 3.9 ± 1.8 ex vivo ). [ 18 F]FDG uptake correlated with plasma total cholesterol levels. Conclusions Atorvastatin therapy did not show cholesterol-independent effects on inflammation in atherosclerotic lesions in Ldlr −/− Apob 100/100 mice, as determined by histology and [ 18 F]FDG PET, whereas a cholesterol-lowering diet intervention was effective.