Type 2 diabetes enhances arterial uptake of choline in atherosclerotic mice: an imaging study with positron emission tomography tracer 18F-fluoromethylcholine

Cardiovascular Diabetology

Original Investigation

Seppo Ylä-Herttuala¹  Pekka Saukko²  Matti Jauhiainen³  Jari Metso³  Johanna M. U. Silvola⁴  Sanna Hellberg⁴  Tapio Viljanen⁴  Max Kiugel⁴  Olli Metsälä⁴  Heidi Liljenbäck⁵  Anne Roivainen⁶  Pirjo Nuutila⁷  Juhani Knuuti⁷  Antti Saraste⁸ 

[1] A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70210, Kuopio, Finland;Science Service Center, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, Finland;Department of Pathology and Forensic Medicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland;Genomics and Biomarkers Unit, National Institute for Health and Welfare, Haartmaninkatu 8, 00250, Helsinki, Finland;Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland;Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland;Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland;Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland;Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland;Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland;Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland;Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland;Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland;Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland;Heart Center, Turku University Hospital, Hämeentie 11, 20520, Turku, Finland;

关键词: Atherosclerosis;    Type 2 diabetes;    Positron emission tomography;    Inflammation;    Choline;    Macrophage;    F-fluoromethylcholine;    F-fluorodeoxyglucose;   

DOI  :  10.1186/s12933-016-0340-6

 received in 2015-11-18, accepted in 2016-01-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDiabetes is a risk factor for atherosclerosis associated with oxidative stress, inflammation and cell proliferation. The purpose of this study was to evaluate arterial choline uptake and its relationship to atherosclerotic inflammation in diabetic and non-diabetic hypercholesterolemic mice.MethodsLow-density lipoprotein-receptor deficient mice expressing only apolipoprotein B100, with or without type 2 diabetes caused by pancreatic overexpression of insulin-like growth factor II (IGF-II/LDLR−/−ApoB100/100 and LDLR−/−ApoB100/100) were studied. Distribution kinetics of choline analogue 18F-fluoromethylcholine (18F-FMCH) was assessed in vivo by positron emission tomography (PET) imaging. Then, aortic uptakes of 18F-FMCH and glucose analogue 18F-fluorodeoxyglucose (18F-FDG), were assessed ex vivo by gamma counting and autoradiography of tissue sections. The 18F-FMCH uptake in atherosclerotic plaques was further compared with macrophage infiltration and the plasma levels of cytokines and metabolic markers.ResultsThe aortas of all hypercholesterolemic mice showed large, macrophage-rich atherosclerotic plaques. The plaque burden and densities of macrophage subtypes were similar in diabetic and non-diabetic animals. The blood clearance of 18F-FMCH was rapid. Both the absolute 18F-FMCH uptake in the aorta and the aorta-to-blood uptake ratio were higher in diabetic than in non-diabetic mice. In autoradiography, the highest 18F-FMCH uptake co-localized with macrophage-rich atherosclerotic plaques. 18F-FMCH uptake in plaques correlated with levels of total cholesterol, insulin, C-peptide and leptin. In comparison with 18F-FDG, 18F-FMCH provided similar or higher plaque-to-background ratios in diabetic mice.ConclusionsType 2 diabetes enhances the uptake of choline that reflects inflammation in atherosclerotic plaques in mice. PET tracer 18F-FMCH is a potential tool to study vascular inflammation associated with diabetes.

【 授权许可】

CC BY   
© Hellberg et al. 2016