Effects of atorvastatin and diet interventions on atherosclerotic plaque inflammation and [18F]FDG uptake in Ldlr-/-Apob100/100 mice.
Atherosclerosis
; 263: 369-376, 2017 08.
Article
en En
| MEDLINE
| ID: mdl-28457625
ABSTRACT
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-/-Apob100/100).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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedades de la Aorta
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Receptores de LDL
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Dieta con Restricción de Grasas
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Inhibidores de Hidroximetilglutaril-CoA Reductasas
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Radiofármacos
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Fluorodesoxiglucosa F18
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Aterosclerosis
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Apolipoproteína B-100
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Placa Aterosclerótica
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Atorvastatina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Atherosclerosis
Año:
2017
Tipo del documento:
Article
País de afiliación:
Finlandia