Effects of atorvastatin and diet interventions on atherosclerotic plaque inflammation and [18F]FDG uptake in Ldlr-/-Apob100100 mice

: Hellberg S, Sippola S, Liljenback H, Virta J, Silvola JMU, Stahle M, Savisto N, Metso J, Jauhiainen M, Saukko P, Yla-Herttuala S, Nuutila P, Knuuti J, Roivainen A, Saraste A

Publisher: ELSEVIER IRELAND LTD

: CLARE

: 2017

: Atherosclerosis

: ATHEROSCLEROSIS

: 263

: 369

: 376

: 8

: 0021-9150

: 1879-1484

DOI: https://doi.org/10.1016/j.atherosclerosis.2017.04.004

Background and aims: Uptake of the positron emission tomography (PET) tracer 2-deoxy-2-[¹⁸F-fluoro-D-glucose ([¹⁸F]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 [18F]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-/-Apob100/100 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, [18F]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, [18F]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). [18F]FDG uptake correlated with plasma total cholesterol levels.Conclusions: Atorvastatin therapy did not show cholesterol-independent effects on inflammation in atherosclerotic lesions in Ldlr-/-Apob100/100 mice, as determined by histology and [18F]FDG PET, whereas a cholesterol-lowering diet intervention was effective.